BeFIT project: Patient-derived models for intratumor functional heterogeneity and its implications for personalized medicine
Our “BeFIT” (Belgium + France + Italy + Taiwan) Team focuses on the study of the inter- and intra-patient heterogeneity, which represents the major driving force for drug-resistance, tumor recurrence, and metastasis. We hypothesize that the phenotypical heterogeneities of tumor and stromal cells may contribute to the adaptation of tumor growth under dynamic and stressful conditions of the tumor microenvironment (TME) via changing its malignant and survival potential, especially under therapeutic and growth stresses. To investigate the evolution of the inter-/intra-tumoral heterogeneity and benefit pre-clinical drug screening, we have established the primary cancer stem cells (CSC)/cancer-associated fibroblasts (CAF) co-culture system and patient-derived xenograft (PDX) models to mimic the TME both in vitro and in vivo. Here, we have identified several important key regulators of cancer plasticity and stemness, drug resistance, and immune checkpoints that are significantly modulated in tumor heterogeneity and evolution under the stress conditionings and could be a benefit to develop novel strategy for the anti-cancer precision medicine.
- Pan-Chyr Yang, National Taiwan University College of Medicine, Taiwan
- Cédric Blanpain, Interdisciplinary Research Institute (IRIBHM) Université Libre de Bruxelles, Belgium
- Patrick Mehlen, Cancer Research Center of Lyon, Centre Léon Bérard, University of Lyon, France
- Sandro De Falco, Institute of Genetics and Biophysics “A. Buzzati Traverso”, Department of Biomedical Sciences, CNR, Italy
Meet Dr. Sheng-Fang Su, an early-career researcher involved in the BeFIT project
Dr. Sheng-Fang Su. Project-Appointed Assistant Professor, Graduate Institute of Oncology, National Taiwan University College of Medicine; YongLin Scholar, NTU YongLin Institute of Health, Taiwan.
How do you think this project has advanced our knowledge about the disease (in concrete, about therapeutic resistance in cancer, a JTC 2014 topic)?
As a young scientist whose study focuses on translational research in tumor biology, I endeavor to integrate the genomic/epigenomic platforms on the patients-derived models, aiming to overcome the unmet needs in anti-cancer treatment. To our knowledge, tumor grows in and co-evolutions with the tumor microenvironment (TME) with a dynamic and heterogeneous property. The complexity of crosstalk between cancer cells/cancer stem cells (CSC) and the stromal niche leads to the difficulty in curing cancer. Our goal of studying the intratumor heterogeneity to explore the mechanisms/roles of cancer cell plasticity and cancer stemness on drug resistance and tumor recurrence well fit the aim of JTC 2014 TRANSCAN-2 at "Translational research on human tumor heterogeneity to overcome recurrence and resistance to therapy". By our ambitious teamwork using patient-derived models to mimic TME both in vitro and in vivo, this project could improve the understanding of the cue of intra-tumorous heterogeneity and help develop the personalized treatment for cancer patients.
What TRANSCAN-2 funding has meant to you to carry out / to be part of the project?
With the support of TRASCAN-2, I had the opportunity to work together with the BeFIT teammates, to share the enthusiasm towards science, which is fulfilling and beyond the funding.
How has the transnational collaborative aspect of the project contributed to project success?
“Be fit” our goal - the transnational collaboration of BeFIT team brings scientists and clinicians across countries together to study tumor biology, from bench work to the clinic, from basic mechanism approach and modeling to pharmaceutical applications.
It has sparked the chemistry interaction of brain-storming and open-minded thinking towards science. It is amazing what such transnational collaboration has given to us.
To form a tacit and successful team to stimulate scientific collaboration is by no means easy. I would thus recommend a long-term programmatical project organization and a stable funding support that allow this transnational collaboration could continue in the future.