Competitive Funded Projects
Competitive Funded Ongoing Projects
INTERNATIONAL
PROJECTS FUNDED BY EU (EUROPEAN UNION)
AIDA – An Artificially Intelligent Diagnostic Assistant for gastric inflammation
Funding agency: EU (HORIZON-HLTH-2022-STAYHLTH-02-01, ID: 101095359) & UK Research and Innovation (ID: 10058099); Budget: 6.33M€ (2023-2026); PI@IPO Porto and WP leader: Mário Dinis-Ribeiro, MD, PhD
Most cases of gastric cancer (GC) are detected at a late stage, when patients have a median life expectancy of about a year. Diagnosing people at risk of developing GC at the pre-symptomatic stage, typically chronic gastric inflammation, could significantly improve the outlook.
Artificial intelligence (AI) can help clinicians make sense of their own data by automating much of the treatment and analysis, which require manual work and years of experience. But it can do more: it can bring together available data from various sources into a vast data lake and cross-correlate the data to derive a ‘risk score’ for gastric cancer and shed light on the mechanisms of its evolution.
AIDA aims to do just that. It helps researchers understand the mechanisms that trigger gastric oncogenesis, helps clinicians diagnose precancerous inflammation at the earliest possible stage, suggests personalised therapeutic strategies for treatment and follow-up, and makes personalised recommendations for monitoring patient health status, thus contributing to gastric cancer prevention.
This places AIDA squarely on Europe’s agenda of ‘Staying healthy in a rapidly changing society’. AIDA unites some of Europe’s leading authorities in the field of gastric inflammation, gastric cancer, leading AI and machine learning experts, experts on data governance and privacy, representatives of the public administration and patient advocates. AIDA also has strong ties with the industry.
After the project, the results will live on in a foundation that acts as a transnational focal point for chronic gastric inflammation — and GC in general. We hope that the solid, inclusive design principles of AIDA, its societal relevance and its durability will spawn a vigorous ecosystem around chronic gastric inflammation, its understanding and its treatment. And we hope that it will inspire other data collaboratives in health — for other chronic inflammations, other forms of cancer or other ailments altogether.
https://www.aidaeuproject.org/about/
CCI4EU – Comprehensive Cancer Infrastructures for the European Union
Funding agency: EU (4 EUROPE-HORIZON-MISS-2022-CANCER-01-02, ID: 101103746); Budget: 57K€ (2023-2026); PI@IPO Porto: Rui Henrique, MD, PhD; Coordinators: Carla Finocchiaro, Valentina Lungheu and Maurizio Cicero – Organisation of European Cancer Institutes (OECI-EEIG)
The aim of the CCI4EU consortium is to strengthen the research capacities of Comprehensive Cancer Infrastructures, by: defining CCI maturity model; designing tailored Capacity Building Programme interventions; delivering online training courses; implementing targeted onsite interventions; disseminate, exploit and report results.
CHIP-AML22 – Improved diagnostics and survival for all children with Acute Myeloid Leukemia treated within the NOPHO-DB-SHIP consortium: a cross-European collaboration
Funding agency: EU4Health (101079988 EU4H-2021-PJ2); Budget: 193K€ (2022-2025); PI@IPO Porto: Vítor Costa, MD; Coordinator: Elise Witthoff, MD, PhD (Sweden)
The CHIP-AML22 project seeks to implement new diagnostic techniques for Acute Myeloid Leukemia (AML) to improve the treatment of patients with these diseases. This consortium seeks to:
– Perform the genetic profile of AML cells to better stratify the risk group of patients;
– WGS and RNA seq analysis to incorporate and improve patient treatment;
– The implementation and evaluation of the response to treatment of both methods during and after treatment, across the consortium.
HENKO NET – Innovation and Digital Technologies for Social and Health Palliative Care at home
Funding agency: co-financed by EU and European Regional Development Fund (ERDF); Budget: 158K€ (2024-2026); PI@IPO Porto: Maria Paula Silva, MD
In several European countries such as Spain, France and Portugal, only a portion of people in need of palliative care (PC) actually receive it. However, PC are essential in controlling symptoms, providing relief, and respecting people’s dignity and as such are an ethical obligation. The significant number of patients needing PC would like to receive them at home, which constitutes an increase in well-being.
HENKO means in Japanese a profound and transformative change. Thus, this project seeks to establish a community of knowledge to strengthen CP systems and lead to organizational change. HENKO NET aims to promote innovation and the adoption of innovative digital technologies so that continuous care is possible at patients’ homes and in rural areas.
The partners in this project will seek a joint strategy to promote innovative advanced training and exchange of best practices in new care models and the adoption of effective digital technologies among healthcare professionals.
The most innovative result expected from this project will be the development of the HENKO platform based on artificial intelligence for the early detection of the need for CP and the anticipation of unwanted events (medical or social). This is expected to significantly improve the organization of care with more effective monitoring at home and a reduction in hospitalizations.
Patients, families and professionals will be actively involved in this development and will be piloted with 100 patients to determine its effectiveness and efficiency. Cooperation between beneficiaries from the three countries (SP, FR and PT) is essential, since innovation in this area is very scarce, so expanding the work scenario at a transnational level will provide sufficient knowledge to develop solutions.
https://interreg-sudoe.eu/en/piloto-proyecto-27/piloting-the-ai-based-henko-predictive-system/
MindGaP – Bridging the gap between Mind, Brain and Body: Exosome role and monitoring – in collaboration with UCoimbra, School of Engineering of IPP and European universities (LINU, VTT, and UOULU)
Funding agency: EU (H2020-FETOPEN-2018-2019-2020-01; ID: 829040); Budget: 799K€ (2019-2024); PI@IPO Porto: Rui Henrique, MD, PhD; Co-PI and WP leader: Carmen Jerónimo, PhD
MindGAP looks for sensitive health indicators among exosomes that circulate throughout the body and that may change under disease. To this end, the possibility of using MINDFULNESS meditation as a mind-related tool to control the cargo of exosomes is explored. If meditation is successful in changing the behavior and attitudes of many people, it means that the exosomes cargo may be changed through this process. The obtained knowledge aims at opening doors to an innovative device that may be used by everyone to understand his/her health status.
ONCOSCREEN – A European “shield” against colorectal cancer based on novel, more precise and affordable risk-based screening methods and viable policy pathways
Funding agency: EU (HORIZON-MISS-2021-CANCER-02, ID: 101097036); 12.97M€ (2023-2026); PI@IPO Porto: Mário Dinis-Ribeiro, MD, PhD
A multilevel campaign to boost colorectal cancer screening.
Population-based screening for colorectal cancer (CRC) is recommended in the EU. Accounting for 12.4 % of all cancer deaths, only one in seven EU citizens participate in screening programmes. The EU-funded ONCOSCREEN project aims to reverse this trend by promoting accurate, non-invasive, cost-effective screening tests based on new technologies and an increased awareness on the disease. Personalised approaches for screening are needed to consider genetic and other socioeconomic variables and environmental stressors. With this in mind, the project will develop a risk-based, population-level stratification methodology for CRC to account for genetic prevalence, socioeconomic status and other factors. Bringing together a 38-partner consortium, the project is in line with Horizon Europe’s Cancer Mission.
ONCOVALUE – Implementing value-based oncology care at European cancer hospitals: An AI-based framework for assessing real-life effectiveness of novel cancer therapies in real-time
Funding agency: EU (ID: 101095245); Budget: 424K€ (2022-2026); PI: Johanna Mattson – HUS Helsinki University Hospital; Co-lead of WP4: Luísa Lopes-Conceição, PhD
The ONCOVALUE consortium aims to unlock the full potential of Real-World Data and Real-World Evidence to maintain the affordability and sustainability of the healthcare system or the treatment of cancer. The project aims to increase the capabilities of European cancer hospitals to easily and quickly collect, harmonize and analyze high-quality Real-World Data in real-time and by developing an AI-based framework. These resources and tools will allow the effective use of data and quality frameworks, for the continuous development of treatments, improvement of results, and support the health regulatory and health technology assessment (HTA) bodies to adopt RWD-driven methodologies in their decision-making on cost-effectiveness of novel cancer therapies.
PAINLESS – Pain relief in palliative care of cancer using home-based neuromodulation and predictive biomarkers
Funding agency: EU (HORIZON-HLTH-2021-DISEASE-04, ID: 101057243); Budget: 5.95M€ (2022-2027); PI@IPO Porto: Rui Medeiros, PhD
Project Team: Universidade de Santiago de Compostela, IPO Porto, Servizo Galego de Saude, Universitaets medizing Goettingen, Aalborg Universitet, Hospice Casa Sperantei, Technion -Israel Institute of Technology, Institutul Oncologic Dr. Alexandru Trestioreanu Bucuresti, European Association of Palliative Care, European Cancer Patient Coalition, Neuroconn Gmbh, Betthera S.r.o., Software Imagination &Vision Srl, Qst.lab, Mentalab Gmbh, Association Europeenne des Ligues Contre Le Cancer Asbl
More than 50% of cancer patients develop pain before death: 80% can be treated with drugs, but 20% show a low response or have serious adverse effects. Although non-pharmacological interventions such as neurosurgical procedures have been tested, these alternatives are not a preferred option to treat cancer pain due to their high cost, risk, invasiveness and not always proven efficacy. PAINLESS addresses a core component of pain relief, by using an innovative, evidence-based approach. The objective is to adapt and implement a novel, cost-effective, home-based intervention based on neuromodulation to reduce pain and improve quality of life of cancer patients with chronic pain. On the assumption that treatment of chronic pain can benefit from research on the brain mechanisms of pain, we will first attempt to improve our understanding of the role of central pain modulation. The project will be organized in 3 studies: 1) A cohort, longitudinal study to explore whether the biomarkers of central pain modulation mechanisms can be predictive of the future occurrence of chronic pain in cancer patients; 2) A cross-sectional study to characterize and stratify cancer patients with vs. without chronic pain; 3) A pilot study to assess the feasibility an efficacy of at-home delivery of transcranial low intensity electric stimulation (tES) for the palliative care of cancer patients suffering from pain PAINLESS will develop a customized web portal to share knowledge and to improve management of the patients; perform technoeconomic analyses and Health Technology Assessment of the solution; analyze the possibilities of implementation in different European healthcare systems and results exploitation; and undertake an ambitious dissemination and communication strategy. We will also propose a wide range of measures to ensure compliance with the highest ethical standards.
https://palliativeprojects.eu/painless/
PCM4EU – Personalised Cancer Medicine for Europe
Funding Agency: EU (EU4Health, ID: 101079984 EU4H-2021-PJ15); Budget: 3.68M€ (2023-2024); PI@IPO Porto: Rui Henrique, MD, PhD (WP Leader) & Júlio Oliveira, MD; Coordinator: Hans Gelderblom, MD, PhD (Netherlands)
Personalised Cancer Medicine for Europe (PCM4EU), is a project funded by the EU4Health Programme with partners from 15 countries across Europe.
The success of Precision Oncology depends on access to adequate molecular diagnostics and access to clinical trials to move towards implementation. The PCM4EU consortium aims to improve inequalities in access to PCM currently existing between and within EU countries and increase survival and quality of life of cancer patients in the EU using PCM based on best practices.
The PCM4EU consortium has an established experience in implementing molecular diagnostics coupled with investigator-initiated drug repurposing PCM trials in European countries, based on the experience of the Drug Rediscovery Protocol (DRUP) trial developed in the Netherlands. These projects effectively act as an ‘implementation device’ for PCM and aim to expand access to drugs besides generate clinical evidence; PCM4EU aims to increase the European reach of this network. This consortium will evaluate current standards and will provide best practice guidelines and recommendations on state-of-the-art genomics diagnostics, implementation and interpretation. Through harmonisation and collaboration the consortium will enable evidence generation for rare mutations/tumour types collecting data simultaneously in multiple countries to obtain faster answers and also, will facilitate interpretation of molecular and clinical data. Cross-border access to PCM clinical trials is another focus points of this consortium, together with the promotion of education for all stakeholders, including physicians, pathologists, patients and decision makers.
https://www.matrix-fkb.no/en/pcm4eu/home
PRIME-ROSE – PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials
Funding Agency: EU (ID: 101104269 HORIZON-MISS2022-CANCER-01); Budget: 5.97M€ (2023-2028); PI@IPO Porto: Rui Henrique, MD, PhD; Coordenador: Kjeitel Tasken, MD, PhD (Norway)
PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials (PRIME-ROSE) is the next step in the evolution of PCM4EU project, focusing on the development and implementation of investigator-initiated “DRUP-like” clinical trials in participating institutions. The main objective of these trials is to assess the efficacy and toxicity of commercially available, targeted anticancer drugs for the treatment of advanced cancer presenting a potentially actionable alteration. The trials incorporates three subsequent stages, opening according to the success of current cohorts. The main goal of PRIME-ROSE is to increase access to optimised and affordable treatment interventions that prolong life and increase cancer patients’ quality of life. This project will generate clinical evidence and evaluating effectiveness of PCM strategies, promoting evidence-based treatment interventions that improve outcomes in cancer care. Additionally this consortium will work together with regulators, policymakers, payers, healthcare providers and patient advocacy groups to implement evidence-based PCM in routine practice, facilitating implementation of the results into the healthcare system in a cost-effective way for future patients.
https://www.matrix-fkb.no/en/prime-rose/home
PROSTAMET – A Comprehensive Translational Research and Training Pipeline Harnessing Lipid Metabolism to Improve Prostate Cancer Management and Educate Young Researchers in Tackling Complex Disease
Funding agency: EU (HORIZON-MSCA-2022-DN-01, ID: 101120283); Budget: 243K€ (2024-2027); PI@IPO Porto: Carmen Jerónimo, PhD; Coordinator: Johannes Swinnen, PhD (KU Leuven, BE)
In the face of complex multifactorial diseases, such as cancer, and the challenges posed by our aging society, the translation of technological advancements into personalised and cost-effective treatments remains a pressing concern for the scientific community. With the support of the Marie Skłodowska-Curie Actions, the PROSTAMET project will create an immersive Doctoral Network (DN) dedicated to training the next generation of researchers in tackling these types of diseases. With a focus on prostate cancer, the project aims to bridge the gaps in translational research by exploring the untapped potential of altered lipid metabolism. By harnessing a transdisciplinary mindset and education, the project aims to establish a unique lipid-focused research pipeline.
TOGAS – TOwards GAstric cancer Screening implementation in the European countries
Funding agency: EU (EU4Health, ID: 101101252); Budget: 11.34M€ (2023-2026); PI@IPO Porto and WP leader: Mário Dinis-Ribeiro, MD, PhD
No effective screening modality to prevent gastric cancer is available in Europe. Elimination of H.pylori bacteria is expected to decrease the mortality by 40%; another approach is early is detection of precancerous lesions for surveillance.
The general objective of TOGAS is to provide the missing evidence-based knowledge to be further transferred to design plan and implement appropriate gastric cancer prevention across the EU. The results from this project will aid policy makers in incorporating gastric cancer screening into their healthcare priorities while balancing its effectiveness, feasibility and acceptability with long-term potential adverse effects.
TOGAS has 3 specific objectives: 1) Assessment of state of play as well as the needs of MSs and target populations in gastric cancer prevention, including information on ‘opportunistic’ screening initiatives organised in public and private setting. 2) Assessment of the appropriateness of various gastric cancer screening modalities for the use in the EU. 3) Assuring the sustainability of the results by an effective dissemination strategy and coordination of the methodology with the approaches used within the EU, including with the European Guidelines and Quality Assurance Schemes.
TOGAS will involve three pilot studies, each designed to address specific aspects of gastric cancer screening and early detection. Cost effectiveness modelling and addressing medical ethics aspects will be an important integral part of the project.
To disseminate widely project results TOGAS will organize three highly visible conferences inviting the key stakeholders and MS representatives as well as a high-level conference together with other cancer screening projects.
The TOGAS consortium unites 18 partners and 3 associated partners representing higher educational institutions, research structures, clinics and wider CSO from 14 member states.
OTHER FUNDING AGENCIES
BENCHISTA – International benchmarking of population-based childhood cancer survival by stage at diagnosis
Funding agency: Children with Cancer UK; Budget: 350K£ (2021-2024); PI: Kathy Pritchard-Jones, MD, PhD & Gemma Gatta, PhD; PI@IPO Porto: Ana Maia Ferreira, MD
The BENCHISTA, is a research collaboration between multiple population-based cancer registries (PBCRs) within and outside Europe. The project is designed to understand the reasons of variation in childhood cancer survival rates between countries and to highlight any areas that require improvement.
Also, the project aims to encourage the application of the Toronto Staging Guidelines (TG) by a large number of European and non-European cancer registries (CRs) for the most common solid pediatric cancers. The project focuses on: medulloblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, and Wilms Tumor. More than 60 CRs will collect information from these types of tumors, diagnosed between 2014-2017, will assign the Toronto Stage at diagnosis and collect other relevant data about the tumor prognosis and survival.
https://www.ucl.ac.uk/child-health/research/developmental-biology-and-cancer/benchista-project
SPECTA – Screening Cancer Patients for Efficient Clinical Trial Access
Funding agency: Alliance Healthcare; Budget: 250€ enrolled patient confirmed as eligible (2019-); PI@IPO Porto: Júlio Oliveira, MD
SPECTA is a collaborative European platform from EORTC (EORTC Protocol 1553, NCT02834884), created to promote development of translational research projects in Europe, mainly focusing on the biological aspects of cancer, including molecular profiling and personalized therapy. As several sub-projects are in the Protocol pipeline, there is a constant update regarding which ones are recruiting, in the final analysis or even in development.
The opportunity to learn more about the integration of comprehensive molecular profiling in the management of cancer patients, the possibility to generate relevant translational and clinical evidence by participating within a European Collaborative Project and the opportunity to offer additional treatment strategies to our cancer patients motivated the IPO Porto team to be fully committed with SPECTA. As this Project became an important and strategic instrument, IPO Porto was even considered as SPECTA Best Recruiter in early 2020, due to the active enrolment of patients in three downstream projects (1759 AYA, 1743 Arcagen and 1828 IMMUcan).
https://spectaplatform.org/projects/
UCIPredict – Circulating tumour microenvironment components as Urothelial Cancer Immunotherapy Response Predictors – in collaboration with CIEMAT (Spain)
Funding agency: TRANSCAN-3, ERA-NET, Sustained collaboration of national and regional programmes in cancer research (JTC 2021) co-funded by the European Commission/DG Research and Innovation; Budget: 99K€ (2023-2025); PI@IPO Porto: Carmen Jerónimo, PhD; Coordinator: Marta Dueñas, PhD (CIBER, SP)
UCIPredict will develop an innovative and reliable urine and blood-based biomarker test for response prediction to immunotherapy IT and tumour recurrence, using non-invasive techniques measuring circulating biomarkers from tumour and tumour microenvironment. Implementation of liquid biopsy biomarkers will improve diagnosis, prognosis and prediction of IT response in UC patients. The main objective of this project is to identify molecular and cellular signatures from urine and blood samples to develop a robust and reproducible laboratory tool for personalized therapy and IT response prediction in UC patients. We will 1) Identify potential molecular targets to guide IT treatments in UC, 2) Detect circulating tumour cells (CTCs) and tumour hybrid cells (THCs) in IT treated and metastatic patients and 3) Evaluate immunomodulation for IT outcome.
https://transcan.eu/output-results/funded-projects/ucipredict.kl
NATIONAL
PROJECTS FUNDED BY FCT (FOUNDATION FOR SCIENCE AND TECHNOLOGY
AFRICA – Sub-Saharan Tumor Line Panel: From Patient-Derived Cells to Specialized Population Treatment of Cancer in African Ancestry
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/BIA-MOL/3986/2021); Budget: 250K€ (2022-2024); Co-PI: Lúcio Lara Santos, MD, PhD
The AFRICA project aims to develop the first bank of primary cells derived from cancer patients originating from sub-Saharan Africa, enabling the characterization of specific molecular phenotypes of individuals of African descent and the adjustment of treatment for these populations.
BioFaeC – Novel faecal biomarkers for early detection of precancerous lesions and Cancer: Improving the current model for colorectal cancer screening
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (2022.09051.PTDC); Budget: 50K€ (2023-2024); PI: Mário Dinis-Ribeiro, MD, PhD; Co-PI@IPO Porto (GPTE): Luís Lima, PhD
One of the biggest challenges in early cancer diagnosis and prognosis is the lack of reliable biomarkers to accurately identify patients at an increased risk of malignant progression. The development of an accessible non-invasive screening method to detect a panel of biomarkers that accurately identify adenomas at risk of malignant progression will greatly advance the early detection of CRC capacity over currently approved screening approaches. Although this is a hot topic, most works often disregard the detection of advanced adenomas, only focusing on CRC, precluding the diagnosis at earlier stages of disease. Hence, BioFaeC aims to identify a reliable panel of biomarkers to improve the accuracy of CRC detection and validate their feasibility as a non-invasive screening tool.
BioFaeC is an exploratory project, granted in the 2022 FCT Call for R&D Projects in All Scientific Domains and stems from the IPO Porto and i3s research consortium (P.CCC Raquel Seruca). It officially started in February of 2023 and will run for 18 months. At IPO Porto and in a collaborative effort, this innovative project is under development at the PRECAM and Experimental Pathology and Therapeutics Groups.
CAGED – Computer Assisted Gastric Cancer Diagnosis
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/EEI-EEE/5557/2020); Budget: 249K€ (2021-2024); PI: Miguel Coimbra, PhD (INESC TEC) & Mário Dinis-Ribeiro, MD, PhD
Gastric cancer is the third deadliest worldwide and minimally invasive screening and gastrointestinal endoscopy play a primary role for early diagnosis, crucial for improving survival rates. However, due to technical and cognitive factors, the probability of a false diagnosis caused by human error is possible.
Thus, the main goal of this study is to develop computer vision-based technologies to automatically analyze videos and images obtained through non-invasive gastrointestinal endoscopies.
Artificial Intelligence, and more specifically Computer Vision, has the potential to mitigate the limitations that currently exist, by providing automated endoscopy assessment tools that can not only support physicians in the detection and characterization of gastric cancer lesions, but can also monitor the quality of the endoscopy itself.
CancerCOV – The impact of the COVID-19 pandemic on the diagnosis, treatment and survival of cancer patients
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (EXPL/SAU-EPI/1606/2021); 49,5K€ (2022-2024); PI: Luísa Lopes-Conceição, PhD; Co-PI: Samantha Morais, PhD
This project aims to study the impact of the COVID-19 pandemic on the diagnosis, care and survival of cancer patients from IPO-Porto throughout the pandemic, by comparing 3 periods, covering the 3 waves after the outbreak began in Portugal.
CyclicCell – Cyclic loading effects in bladder cancer cells
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (ID: PTDC/EME-APL/1342/2020); Budget: 249K€ (2021-2024); PI: João Ferreira, PhD (INEGI); PI@IPO Porto: Carmen Jerónimo, PhD
In bladder neoplasms, it is not clear what distinguishes cancer cells that invade the muscle layer from those that do not, nor how bladder function affects disease persistence and metastasis formation. Given the fact that the bladder is exposed to intrinsic cyclic pressure, there is a possibility that this is a significant physical factor that could control the epithelial-mesenchymal transition (EMT) in bladder cancer, predisposing cells to invasion.
Therefore, the goal of the CyclicCell project is to understand the mechanics and structure of bladder cancer cells in mechanical environments similar to those in vivo and to understand how these physical properties affect disease progression. The conclusion of this study will identify physical targets to prevent or mitigate EMTs in bladder cancer. This work will also develop a platform to assess the status and impact of mechanical stimuli on other types of cancer.
EpImmunePCa – On the crossroads of Immuno-Epigenetics for targeting advanced Prostate Cancer – in collaboration with INEB/i3S
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (2022.04809.PTDC); Budget: 250K€ (2023-2025); PI: Margareta Correia, PhD; Co-PI: Rui Henrique, MD, PhD
The overall objective of this project is to define a transcriptional and epigenetic profile of cytotoxic tumor-infiltrating lymphocytes, which can be targeted to increase the efficacy of immunotherapies, especially in metastatic castration-resistant prostate cancer (mCRPC), with the translational aim of combining epi-drug pre-conditioning and adoptive cell transfer targeting PCa tumor-associated molecules.
GLYCOTARGET – A new frontier in extracellular vesicle-mediated cancer immunomodulation
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (ID: PTDC/MEC-ONC/0491/2021); Budget: 248K€ (2022-2024); PI: Celso Reis, PhD (i3S); PI@IPO Porto: Carmen Jerónimo, PhD
Currently, immunotherapy for treatment of gastrointestinal cancer (GIC) is effective in a small percentage of patients. Thus, more effective and novel targets to reduce immunosuppression are imperatively required to increase as well as improve the existing therapeutic range. Extracellular vesicles (EVs) secreted by tumor cells are crucial mediators of intercellular communication, contributing to an immunosuppressive pro-tumorigenic microenvironment, which favors disease progression. Thus, EVs are a clinically appealing source of tumor antigens for cancer vaccination, however, due to immunosuppressive nature, new approaches are required to increase its therapeutic efficiency. It is hypothesized that immunosuppressive glycans in EVs derived from the tumor can be targeted to achieve an efficient anti-tumor immune response. This project aims to create novel therapeutic approaches by the identification as well as targeting of immunosuppressive glycans present in EVs from the tumor.
iNNOV Sensing – A pilot cognitive-behavioral internet intervention to detect, treat, and monitor anxiety and depression in breast cancer survivors based on multimodal active and passive sensing data
Funding Agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (2022.15591.CMU); Budget: 70K (2024); PI: Cristina Mendes Santos, PhD
The aims of this project are:
1) To explore the acceptability and feasibility of iNNOVBC and the collection of passively sensed smartphone and wearable data in BCS; 2) To develop an Intelligent solution to assess anxiety and depression, detect changes in its severity, and predict its course in BCS and; 3) To assess the preliminary efficacy of INNOVBC in improving anxiety and depression, and psychological flexibility, fatigue, insomnia, sexual dysfunction, and Health-Related Quality of Life (HRQoL) in BCS when compared to treatment as usual (TAU) in a waiting-list control group (WLC).
PCaEVision – Decoding the role of extracellular vesicles in prostate cancer bone metastasis – in collaboration with Champalimaud Foundation and CNIO (Spain)
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology); Budget: 50K€ (2023-2024); PI: Vera Constâncio, MSc; Co-PI: Hector Peinado, PhD
The overarching aim of PCaEVision is to foster the knowledge of physiopathological processes in PCa bone metastasis development by tackling the contribution of PCa derived extracellular vesicles (EVs) for bone metastasis development in vivo.It is expected that PCaEVision will contribute with: i) the elucidation of the role of EVs produced by PCa primary tumors in bone metastatic disease development, opening a venue for future studies aiming to characterize the molecular alterations caused by PCa derived EVs during bone metastasis initiation and progression, and ii) the identification of new potential biomarkers of PCa aggressive disease. Ultimately these findings could contribute to the improvement of health and survival of PCa cancer patients.
PRUNE2 – PRUNE2 gene as a novel dual-role biomarker for prostate cancer inherited predisposition and therapy response
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (2023.01928.RESTART); Budget: 49,8K€ (2023-2025); PI: Andreia Brandão, PhD
Building on previous findings, this project aims to combine genomic, transcriptomic, and computational approaches to establish PRUNE2 as a new prostate cancer susceptibility gene and evaluate its potential as a predictive biomarker.
RESOLVE – Rational Design of Multivalent Glycocode-Inspired Nanovaccines for Gastric Cancer Immunotherapy
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (10.54499/PTDC/MED-OUT/2512/2021); Budget: 50K€ (2022-2024); PI: José Alexandre Ferreira, PhD; Co-PI: Juan Lasarte, PhD (CIMA, Spain)
RESOLVE aims at a comprehensive interrogation of the gastric cancer glycoproteome for unique molecular signatures to improve patient stratification. It also plans to translate clinically relevant signatures into innovative cancer glycovaccines exploiting proprietary cutting-edge glycoengineered nanovehicles. These new generation of glycosylated vaccine vehicles can specifically deliver immunogenic cargos to antigen presenting cells, unleashing otherwise compromised immune responses against cancer cells. The objective is to setup the pre-clinical basis for an innovative immunotherapy for cancer.
REVERENT – Pre-clinical Validation of a Glycocode-inspired Vaccine for Bladder Cancer Immunotherapy
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (2022.03621.PTDC); Budget: 50K€ (2023-2024); PI: Andreia Peixoto, PhD; Co-PI: José Alexandre Ferreira, PhD
The project aims to validate a glycovaccine for bladder cancer in a pre-clinical context, using relevant animal tumor models, with the translational intent for clinical studies.
RISE2020 – Rede de Investigação em Saúde: do Laboratório à Saúde Comunitária – RISE
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (LA/P/0053/2020); Budget: 375K€ (2021-2025); PI@IPO Porto: Carmen Jerónimo, PhD & Fernando Schmitt, MD, PhD (FMUP)
Projects funded by LPCC (Portuguese Cancer League)
CO(r)RECT Me – Metastatic COloREctal Cancer Treatment Pathway
Funding agency: Liga Portuguesa Contra o Cancro (LPCC; Portuguese Cancer League); Budget: 13,5K€ (2024-2025); PI: Teresa Monjardino, PhD & Dânia Marques, MD
Survival of patients diagnosed with metastatic colorectal cancer (mCRC) varies widely across the EU. The protocols for mCRC are highly variable and decided by multidisciplinary teams. Therefore, a thorough analysis of clinical practices among EU countries may be of interest to start analyzing differences in outcomes. The CO(r)RECT Me project bring together a team from different European countries to study differences in clinical outcome and to evaluate correlation with the pathway of cure and additional emerging variables.
ISCCP – Incidence and survival for childhood cancer in Portugal from 2010-2020: a nationwide population-based study
Funding agency: Liga Portuguesa Contra o Cancro (LPCC; Portuguese Cancer League); Budget: 15K€ (2024-2025); PI: Teresa Monjardino, PhD
The primary objective of this study is to analyze childhood cancer incidence and survival rates and trends for the period 2010-2020, in Portugal, by sex, age, cancer site and region. As secondary objective we will evaluate the risk of multiple cancers in a cohort of patients. With this project we hope to obtain point estimates and updated temporal trends of childhood cancer incidence and survival. These indicators are decisive for planning and implementation of cancer prevention and control strategies.
OTHER FUNDING AGENCIES:
OnCOVac.PT – Evaluation of the Immunologic Response to COVID-19 Vaccination in Oncological Patients
Funding agency: AstraZeneca; Budget: 460K€ (2022-2024); PI: Júlio Oliveira, MD; Co-PI: Rui Medeiros, PhD
The Portuguese Health Authorities declared the existence of active community transmission of COVID-19 virus since 26 of March 2020 and state of emergency was declared in order to combat the coronavirus pandemic. Reported illnesses have ranged from very mild to severe, including illness resulting in death. Cancer patients are more susceptible to infection compared to healthy people and noncancer patients. That predisposition has been historically related to the systemic malignancy-related immunosuppressive state and to active disease-oriented treatments, such as chemotherapy, radiotherapy and surgery. Despite the limited data, medical organizations and cancer experts indicate for vaccination most cancer patients. However, more data are needed on the safety and efficacy of COVID-19 vaccines, as well as the effect of vaccine booster doses, in people with compromised immune systems. Therefore, it is expected that cancer patients would be more prone to have a weaker response to vaccination. In addition, the non-responders to the vaccine will be at greater risk of developing COVID-19 infection, and subsequent complications. The importance of this issue is growing in the scientific community since there are new anti-COVID-19 therapies emerging that could benefit the non-responders and prevent them from developing aggressive forms of infection. Therefore, it is imperative to study the immunological response of cancer patients to booster doses of COVID-19 vaccination to get more insight on the percentage of non-responders and to study new molecular, genetic and epigenetic biomarkers that enable the distinction between responders and non-responders.
Building on previous findings, this project aims to combine genomic, transcriptomic, and computational approaches to consolidate PRUNE2 as a novel cancer predisposing gene for prostate cancer, and to evaluate its potential as a predictive biomarker.
Competitive Funded Concluded Projects
INTERNATIONAL
PROJECTS FUNDED BY EU (EUROPEAN UNION)
4.UNCAN.eu – A Coordination and Support Action to prepare UNCAN.eu platform – in collaboration with Institut National de la Santé et de la Recherche Médicale (France)
Funding agency: EU (HORIZON-MISS2021-UCAN-01, ID: 101069496); Budget: 2.99M€ (2022-2023); PI@IPO Porto: Maria José Bento, MD, PhD
The blueprint for UNCAN.eu will propose to set up a European Federated Cancer Research data hub and to generate a series of use cases, addressing major challenges in cancer research. These ambitious and innovative, but realistic and focussed, use cases will be cross-border and trans-disciplinary research programmes built in a problem-solving manner. Results of these use cases will feed the Cancer Research data hub with findable, accessible, interoperable, and re-usable (FAIR) cancer research data. These research data will be combined with patient health and any other relevant data (e.g., from longitudinal cohorts, geographical observations, consumer and lifestyle data) at an unprecedented scale. UNCAN.eu that will bring all relevant players and information together, based on existing efforts in Europe and beyond.
NATIONAL
PROJECTS FUNDED BY FCT (FOUNDATION FOR SCIENCE AND TECHNOLOGY)
ACCuseD – Kidney cancer detection: translational metabolomics study based on volatile compound profiling
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/SAU-SER/30388/2017); Budget: 240K€ (2018-2021); PI@REQUIMTE: Paula Guedes, PhD, Co-PI: Carmen Jerónimo, PhD
The metabolic profile of CRC will be evaluated in in vitro and ex vivo models with increasing biological complexity: (1) immortalized cell lines of tumor and normal renal cells; (2) tumor and healthy (adjacent) kidney tissue from patients undergoing nephrectomy.
This approach will allow the establishment of a panel of biomarkers that will be subsequently validated in urine from patients with CRC. To study the VOCs profile of CCR, analytical methodologies will be implemented, such as Gas Chromatography coupled to Mass Spectrometry (GC-MS), and multivariate statistical analysis methods for classifying samples into normal or tumor groups and identifying the metabolites responsible by discriminating these two groups with greater sensitivity and specificity.
At the same time, a sensor will be applied to determine volatile compounds based on the electronic nose (e-nose). The two metabolic signatures (GC-MS and e-nose) determined non-target will be interpreted together for the in vitro model and urine.
The project will proceed with validation of candidate biomarkers in urine from ccRCC patients from two different populations to prove biomarker translation. In the end of this project, the validated urinary biomarkers will be patented for the development of a non-invasive diagnostic tool for ccRCC.
EpiMarkGermCell – Development of novel prognostic and predictive epigenetic biomarkers for malignant testicular germ cell tumors
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (POCI-01-0145-FEDER-29043); Budget: 240K€ (2018-2021); PI: Rui Henrique, MD, PhD, Co-PI: Carmen Jerónimo, PhD
There is an unmet need for clinically useful tools to assist in prognostication and prediction of cisplatin-resistance of malignant testicular germ cell tumor (TGCT), the most common cancers afflicting young Caucasian men. In this project, we aim to discover and validate novel prognostic and predictive epigenetic-based biomarkers for TGCT, allowing for the delivery of improved patient care. Tissue and liquid biopsies will be made available and tested for altered DNA methylation patterns, modifying/chromatin remodelling enzymes expression and miRNAs transcript levels. Successful candidate biomarkers will be submitted for European patenting. This project builds on the experience of Cancer Biology and Epigenetics Group from IPO Porto in developing epigenetic-based biomarkers for urological cancers.
HyTherCaP – Hydralazine: Testing an off-label effect in Castration-Resistant Prostate Cancer
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (POCI-01-0145-FEDER-29030); Budget: 240K€ (2018-2021); PI: Carmen Jerónimo, PhD, Co-PI: João F Mano, PhD (UA | CICECO)
Prostate cancer (PCa) is one of the most common malignancies worldwide. Most patients that initially respond to androgen ablation therapy, eventually develop castration-resistant (CRPC) disease, entailing widespread metastatic dissemination. CRPC has been related to androgen receptor (AR) pathway deregulation. Aberrant DNA methylation also plays a critical role in emergence of CRPC. Thus, DNA methylation inhibitors (DNMTi) might constitute promising alternative therapies for CRPC management. We reported that hydralazine, a non-nucleoside DNMTi, attenuated malignant phenotype of PCa cells that was particularly impressive in a CRPC cell line harboring AR hypermethylation. We aim to confirm hydralazine’s mechanism of action in CRPC, which putatively involves demethylation-mediated AR re-expression and define a biomarker predictive of response to this therapy, enabling the off-label use of hydralazine in CRPC patient subset displaying AR hypermethylation.
IPOScore – Predicting the risk of complications of surgical treatment and define prognosis of cancer patients through clinical and biopathological data integration
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (DSAIPA/DS/0042/2018); Total Budget: 247K, CI-IPOP Budget: 32K€ (2019-2022); PI: Rafael Sousa Costa, PhD, PI@IPO Porto: Lúcio Lara-Santos, MD, PhD
This project intends to apply an innovative approach based on data-driven modeling that integrates clinical, biopathological and physiological data of patients with cancer to predict the risk of (post-)operative complications. The expected outcome is the creation of an user-friendly online platform, which includes a database to store/manage the data collected in a structured format, computational approaches and prediction models to calculate a specific risk index score for the Portuguese population. The platform will provide an added-value to surgeons in oncological hospitals as an intelligent clinical decision support system.
Nanowar2UrCancer – Sensitization of Urologic Tumors Therapy Driven by Nanotechnology
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/MED-QUI/29800/2017); Budget: 240K; (2018-2022); PI@IPO Porto: Rui Medeiros, PhD; Co-PI: João Prior, PhD (FFUP| REQUIMTE)
Cancer remains one of the major public health problems worldwide. In Portugal, there has been a significant increase in the number of new cases diagnosed over recent years. Additionally, the lack of response or development of resistance to antineoplastic treatments represents the greatest challenge in oncology. The increase in new cases is accompanied by rising treatment costs, which has a significant economic and social impact. Currently, despite substantial investment, innovative drugs often fail due to the early development of resistance by tumor cells. This issue results in a total loss of financial investment from the start of treatment, unfortunately, without any benefit to patients. The same applies to other types of treatment, such as radiotherapy, where infrastructure and equipment investment has been substantial in recent years. Thus, there is an urgent need to optimize the effectiveness of antineoplastic therapies to improve the quality of patient care.
The proposed approach to solve this problem involves combining silver nanoparticles (AgNPs) with the administration of chemotherapy and radiotherapy to maximize the effectiveness of these standard treatments. It is important to note that, alongside the investment in innovative drugs and associated costs, there has been a reduction in costs associated with older therapies such as chemotherapy. AgNPs are easy to synthesize using a green synthesis approach, have low production costs, their cytotoxic effects can be controlled, and they can be designed to target specific receptors on cell membranes. The presence of AgNPs targeted at neoplastic cells will allow for their weakening, making them more susceptible to chemotherapy and radiotherapy. Additionally, the impact of AgNPs on the effectiveness of these treatments could also result in a reduction of the administered doses, thus decreasing associated side effects.
NGS-HPC – Inherited predisposition to prostate cancer: finding the missing heritability by combining exome sequencing and haplotype analyses in a population with strong founder effects
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/DTP-PC/1308/2014); Budget: 196K€ (2016-2019); PI: Manuel Teixeira, MD, PhD
PROTECT – Prehabilitation to enhance cancer treatment in patients with adenocarcinoma of the gastroesophageal junction and the stomach
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (PTDC/SAU-DES/7945/2020); Budget: 250K€ (2021-2023); PI: Lúcio Lara Santos, MD, PhD
The PROTECT project envisions the multimodal prehabilitation of proximal gastric and gastroesophageal junction cancer patients to minimize the burden without compromising the safety and efficacy of anti-cancer treatment.
RISK – New mRNA signatures as risk markers in cancers triggered by tobacco smoking
Funding agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (EXPL/SAU-PUB/1073/2021); Budget: 50K€ (2021-2023); PI: Isabel Pereira Castro, PhD (i3S); Co-PI: Maria José Bento, MD, PhD
RISK aims to identify, validate and explore the potential of new risk markers and therapeutic targets (mRNA signatures diagnostic kit and mRNA vectors) to be used in patients with lung, bladder, and head and neck cancer. Overall, this project will advance current knowledge on mechanisms of disease, will provide new tobacco risk markers and will open novel opportunities for therapeutic intervention to be used in a clinical setting.
SEGMAPP – Role of chromosome segregation machinery in genetic predisposition to prostate cancer
Funding agency: Fundação para a Ciência e Tecnologia (FCT: Foundation for Science and Technology) (POCI-01-0145-FEDER-028245), Budget: 236K€ (2018-2021), PI: Paula Paulo, PhD
The main objective of the project is to clarify whether germline mutations in genes of the chromosome segregation machinery (MSC), found in patients with hereditary/familial prostate cancer (HPC), are involved in the development of this neoplasia. The project has 4 main aims:
- Characterize the profile and frequency of deleterious variants in MSC genes in HPC patients and controls;
- Evaluate the pathogenic potential of all variants in silico using 3D modeling models;
- Clarify the biological impact of recurrent variants using in vitro models;
- Validate the oncogenic potential of the most promising variants ex vivo, using carrier samples.
TOGETHER – Connecting people and systems to support an effective psychosocial adjustment to genetic testing in the context of inherited cancer risk
Funding agency: Fundação para a Ciência e Tecnologia (FCT: Foundation for Science and Technology) (POCI-01-0145-FEDER-030980), Budget: 236K€ (2018-2022) PI@FPCEUP: Célia Sales, PhD, Co-IP: Eunice Silva, PhD
TRIMARKCHIP – Assessing the trifecta of cancer circulating biomarkers: a combined microfluidics platform for detection of CTCs, exosomes and ctDNA
Funding agency: Fundação para a Ciência e Tecnologia (FCT: Foundation for Science and Technology) (POCI-01-0145-FEDER-030831- PTDC/BTM-TEC/30831/2017), Budget: 41K€ (2018-2022) PI@i3S: Fernando J Monteiro, PhD, Co-PI: Carmen Jerónimo, PhD
The proposed project focuses on developing an advanced microfluidics one-chip system for isolation and characterization of three circulating biomarkers present in peripheral blood of cancer patients: Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes. This advanced system will be applied for lung cancer diagnosis, prognosis, assist in treatment selection, and assess cells response to therapy. Lung cancer continues to be the deadliest cancer worldwide, difficult to detect at early stages and in many cases, inaccessible for tissue biopsy. New strategies are needed for early detection of the primary tumor and metastases and correct selection of patient-specific treatments depending on tumor mutations. This system would be a thorough and powerful tool to assess, from a simple blood draw, the complete genetic landscape of the disease, from the primary site to possible metastases, assisting in a continuous, real-time, monitoring of each patient disease.
PROJECTS FUNDED BY ERDF (EUROPEAN REGIONAL DEVELOPMENT FUND)
DCMatters – Combination of Dendritic Cell Vaccine with Immune Checkpoint Inhibitors as First-Line Therapy in Patients
Funding agency: European Regional Development Fund (ERDF) (NORTE-01-0247-FEDER-047212); Budget: 822K€ (2021-2023); PI: Lúcio Lara Santos, MD, PhD
The DCMatters project aims to develop and manufacture a new generation of dendritic cell (DC) vaccines with greater capacity to induce an anti-tumour response, by optimizing the manufacturing method using chemoinformatic tools and validating it in vitro and in vivo.
ESTIMA – Early-Stage Cancer Treatment in The Context Of Molecular Imaging
Funding agency: European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000027); Budget: 3M€ (2016-2019); PI: João Santos, PhD
The ESTIMA project aims to develop a multidisciplinary predictive model of a complete response after neoadjuvant radiochemotherapy for patients with esophageal cancer. Although this study does not change the current treatment approach, knowledge of the individual response may allow a personalized approach to each patient in the future, avoiding unnecessary surgical interventions in patients with a complete response and all associated comorbidities and loss of quality of life. The project involves the participation of several researchers from the institution and also from different groups associated with the Research Center of the Portuguese Institute of Oncology of Porto Francisco Gentil, as well as close collaboration with the Center for Informatics and Systems at the University of Coimbra. The project has two main lines of action: a diagnostic line, in which images obtained by positron emission tomography (PET/CT) are analyzed using advanced algorithms (“data mining”, neural networks, “deep learning”). A second line intends to investigate various types of biomarkers that condition the response to therapy. As a fundamental part of the project, it is also intended to optimize the deposition of radiation dose in these tumors by the new Varian TrueBeam linear accelerator, for which it has already been possible to simulate volumetric radiotherapy treatments (VMAT) using advanced Monte Carlo methods. Several communications have already been presented or are accepted for presentation at national and international conferences.
IMAGE – Individualized Gastric Adenocarcinoma Early Diagnosis and Improved Patients’ Survival: From Liquid Biopsies to a Comprehensive Management Approach
Funding agency: European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000050); Budget: 601K€ (2021-2023); PI: Mário Dinis-Ribeiro, MD, PhD
The IMAGE project aims at uncovering novel cancer biomarkers that can be readily detected by non-invasive methodologies, allowing an early diagnosis of gastric cancer a significant societal problem in Portugal. Together with other patients’ information, the final diagnostic tool tackles the disease in its early development, resulting in enhancing patient’s survival and quality of life (QoL) through less aggressive and invasive therapeutic procedures (see Visual Abstract). Furthermore, it will reduce the health system’s economic burden and potentially the disparities, by empowering citizen, adding information to endoscopy and individualizing management.
The project is structured in three specific lines:
– in RL1, transcriptomic studies will be performed to determine a panel of biomarkers in saliva to non-invasively allow gastric cancer screening and monitoring;
– in RL2, the focus is the concept of functional endoscopy, i.e., the purely morphological/imagiological concept of endoscopy will be challenged by adding the information from biomarkers in the gastric mucus (microbiota);
– and in RL3, a comprehensive clinical decision rule will be developed by integrating a priori data (clinical, endoscopic and molecular) and with this tailored screening to gastric cancer.
This consortium and unique project will promote further gains in this area of research, contributing to answer to a societal responsibility towards a relevant health problem, especially in the North of Portugal. We hypothesize that, all together, our findings will clearly improve the knowledge and technologies available for the early diagnosis of gastric cancer and patients’ surveillance and, due to a clear impact in health-care resources and patients’ burden, will potentially decrease disparities in the access to care by providing the best care to those in need – the final aim for clinical and translational research.
NASYTHOR – Novel Natural and Synthetic Compounds for Treating Hormone Resistant Tumors
Funding Agency: Fundação para a Ciência e Tecnologia (FCT; Foundation for Science and Technology) (NORTE-01-0145-FEDER-024156); Budget: 150K€ (2017-2019); IP: Regina Silva,PhD, Co-IP@IPO Porto: Carmen Jerónimo, PhD
In the Northern region of Portugal, prostate cancer and breast cancer are the most common cancers in men and women, respectively. Despite advances in early detection and treatment, high mortality rates continue to challenge the discovery of new antitumor agents. This project aims to evaluate the antitumor potential of plant extracts, ionic liquids and quinoxalines in hormone-resistant tumors common in the Northern region of Portugal, in this case castration-resistant prostate tumors and estrogen-independent breast tumors. The project involves the in vitro evaluation of the antitumor potential in prostate and breast cell lines in order to select the most promising ones and in vivo using zebrafish as a model, the identification of gene expression by treatment with the selected compounds in order to infer the molecular mechanism of action underlying the cytotoxic effects and the evaluation of the clinical utility of gene expression that can be used to predict therapeutic response and thus serve as a biomarker for clinical management and therapeutic guidance. With this approach, it is expected to identify new anti-tumor compounds targeting the most common and incident tumors in the Northern Region of Portugal.
PRO-DOSE – Device for in-vivo dosimetry in brachytherapy;
Funding Agency: European Regional Development Fund (ERDF) (POCI-01-0247-FEDER-017816); Budget: 716K€ (2016-2018); PI: João Santos, MD, PhD
The project aims to develop an innovative solution to overcome the lack of equipment for dosimetric control of radiotherapy treatments. PRO-DOSE technology allows in-vivo and real-time control of the radiation dose delivered to the patient during breast and prostate brachytherapy treatments, thus ensuring maximum quality and effectiveness.
SIRNAC – Novel Therapies Against Metastatic Colorectal Cancer
Funding Agency: European Regional Development Fund (ERDF) (NORTE-01-0247-FEDER-033399); Budget: 758K€ (2018-2022); PI: Rui Medeiros, PhD
Co-Promotion Project: Phyzat, IPO Porto, INEB
This project refers to a new therapy for metastatic colorectal cancer in the liver, aiming to significantly reduce the impacts of a disease with extremely heavy human and economic costs. This project covers the development phase of the new drug, following a successful discovery phase by the consortium leader, which demonstrated the efficacy of the selected molecules in vitro and in vivo. It includes the development of the selected molecules, the development of the delivery system, and the validation of the clinical and therapeutic relevance, either isolated or combined, of the two new targets.
This project will allow the completion of the development phase and license the program to initiate regulatory trials aimed at the approval of the new therapy.
TeamUP4Cancer – Porto Comprehensive Cancer Center (Porto.CCC)
Funding Agency: European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER072678); Budget: 17,6M€ (2021-2023); PI: Rui Henrique, MD, PhD
The Porto Comprehensive Cancer Centre (P.CCC) consortium, which includes the IPO Porto and the IBMC, INEB, IPATIMUP Institutes, and i3S – Institute for Research and Innovation in Health at the University of Porto, will implement the “TeamUp4Cancer” project in the Northern region. This project has been approved by NORTE 2020 under the Scientific and Technological Research Support System (STRSS).
This research project aims to shorten the scientific discovery cycle in cancer by bridging the gap between basic research and clinical practice through the application of cutting-edge technology and the exploration of early-phase clinical trials, seeking concrete benefits for cancer patients and the faster development of new therapeutic weapons against cancer.
The partners aim to develop in vitro experimental models to assist in patient treatment, validate and explore new biomarkers in tumor tissues, blood, and other tissue samples, and accelerate preclinical studies, facilitating the transition to early-phase clinical studies.
Projects funded by LPCC (Portuguese Cancer League)
EVmiRs4PC – Extracellular Vesicle-Derived microRNAs as Mediators of Treatment Resistance in 3D Spheroid In Vitro Models of Prostate Cancer
Funding Agency: Liga Portuguesa Contra o Cancro – Núcleo Regional do Norte (LPCC-NRN; Portuguese Cancer League – North Branch) (CI-IPOP 13-2022); Budget: 5K€ (2022-2023); PI: Ana Luísa Teixeira, PhD
Prostate cancer (PC) is the second most common malignancy in men worldwide, accounting for 6.8% of cancer deaths. Androgen deprivation therapy (ADT) is frequently used in the treatment of advanced and metastatic PC, as prostate tumors are highly dependent on the androgen pathway for proliferation and progression. This treatment is initially effective, but on average, resistance develops after 2-3 years, leading to castration-resistant prostate cancer (CRPC). Enzalutamide (ENZ) is a second-generation antiandrogen developed for the treatment of CRPC. However, approximately 15-20% of patients exhibit primary resistance, and a high percentage eventually develop resistance to this new agent.
In recent years, microRNAs (miRNAs) have emerged as potential biomarkers in various tumor models. Due to their significant role in regulating gene expression, their dysregulation has often been associated with the acquisition of resistance phenotypes and metastatic forms of the disease. In addition to their potential as diagnostic and prognostic biomarkers, miRNAs have shown great promise as therapeutic agents, either through the use of miRNA mimics or anti-miRNAs (anti-miRs).
Thus, we aim to define an miRNA profile in EVs associated with the acquisition of ENZ resistance and analyze its dynamics during the resistance acquisition process in 3D spheroid in vitro models. Identifying these miRNAs, alongside identifying proteins and their respective signaling pathways, will help elucidate the molecular mechanisms of ENZ resistance. Clinically, this miRNA resistance profile could be applied in the follow-up of patients undergoing ENZ treatment to detect resistance emergence through liquid biopsies and reveal new therapeutic targets. The identification of aberrantly expressed miRNA profiles could also facilitate the development of anti-miR therapy, useful in resensitizing tumor cells to androgen deprivation therapy.
OTHER FUNDING AGENCIES
CIPNETH – The Causes and Consequences of Incomplete Paclitaxel Administration during the Neoadjuvant treatment of Early Triple negative and HER2 positive breast cancer
Funding agency: DIGICORE; Budget: 70K€ (2022-2023); PI: Luísa Lopes-Conceição, PhD; Co-PI: Cláudia Vieira, MD, PhD
Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related deaths among women worldwide. Most patients are diagnosed with early-stage BC (eBC) in which the aim of treatment is to increase survival rates by reducing the risk of metastasis occurrence.
The backbone of neoadjuvant chemotherapy for eBC is the sequential administration of anthracyclines and taxanes. The administration of the initially planned dose-intensity of paclitaxel is frequently hampered by side effects, mainly chemotherapy-induced peripheral neuropathy. Importantly, there is no established strategy to treat or prevent this side effect. This study aims to highlight a potential impact of reduced paclitaxel dose-intensity, in a neoadjuvant context, on the effectiveness of the treatment of patients with triple-negative and HER2 positive eBC, measured by the complete pathological response rate and survival free from invasive disease.
Epidemiological characterization of the population of patients with chronic myeloid leukemia treated at the Porto IPO
Funding agency: Portuguese Association Against Leukemia, Portuguese Society of Hematology and Novartis; Budget: 15K€ (2022-2023); PI: Ana Meireles, MD
The introduction of tyrosine kinase inhibitors (TKI) was revolutionary in the treatment of chronic myeloid leukemia (CML). The focus changed from delaying the progression of the disease to more advanced stages, to obtaining a survival similar to the general population, achieving a profound molecular response and discontinuing therapy while maintaining remission. Furthermore, it is increasingly important to consider the effects of TKIs on patients’ quality of life and patient-reported outcomes in the therapeutic approach. There are several studies on responses and adverse effects in patients with CML. However, the characterization of these patients in Portugal is not yet known. This project’s main objective is to describe the population of patients with CML treated at IPO Porto and, in parallel, to describe adverse effects of TKIs documented in these patients and which patients are candidates for TKI suspension and whether there was a need to resume TKIs.
Immunotherapy in recurrent/metastatic head and neck cancer: real-world data from six European countries
Funding agency: DIGICORE; Budget: 11,6K€ (2022-2023); PI: Rita Calisto, MSc; Co-PI: Cláudia Vieira, MD, PhD
In the last decade, several randomized controlled trials (RCTs) supported the use of anti-PD-1 (programmed cell death protein 1) agents in advanced squamous cell carcinoma of the head and neck (HNSCC) in first and further lines, improving overall survival (OS) compared to standard of care. Nevertheless, the results of RCTs may not be entirely generalized to the real-world population due to the stringent inclusion criteria and the rigid schedule of visits and exams. Real-world data (RWD) may overcome the limits imposed by rigorous design of RCTs and unlock key insights, including those related to underrepresentation in clinical trials. This study aims to describe and compare characteristics and treatments of real-world patients with recurrent or metastatic HNSCC, among seven participating centers in six European countries, by collecting retrospective information on the use of immunotherapy in these patients.
Laserthermia – Synergistic antitumor effect of combined laser thermotherapy and immunomodulators in malignant melanoma
Funding agency: Clinical Laserthermia Systems AB (PI 130-CI-IPOP-125-2019); Budget: 79K€ (2019-2022); PI: Carlos Alberto Palmeira de Sousa, PhD; Co-PI: Lúcio Lara Santos, MD, PhD
The Laserthermia project aims to evaluate the synergistic antitumor effect of laser-based thermotherapy and clinically implemented immunomodulators in poorly immunogenic B16F10 melanoma mouse models.
