Periodic Reporting for period 1 - FUNTRICAN (Functional analysis of thyroid hormone nuclear receptors TRs in human Intestinal Cancer stem cells)
Reporting period: 2019-05-01 to 2021-04-30
The objectives of this Marie Sklodowska Curie Action (MSCA) were to unravel (1) how CRC tumors behave in their hormonal microenvironment by enlarging the current understanding on the molecular mechanism of TRs’ functions in CRC aggressiveness and (2) to evaluate the therapeutic potential of targeting TRa1 and TRb1 activity for designing novel therapies to treat CRC. By developing FUNTRICAN project, our findings further explored the oncogenic role of THs and TRs in CRC where we identified an antagonist role of TRa1 and TRb1 in CRC tumorigenesis and more importantly confirmed that modulating TRa1 and TRb1 activity impact CRC sensibility to conventional therapies opening thereby a new avenue to prevent tumour relapse.
The MSCA fellow obtained a permanent researcher position at the French National Centre for Scientific Research (CNRS) in a prestigious institute in Lyon during the MSCA fellowship, reflecting the positive impact of the MSCA individual fellowship on early career scientists.
The management of the project was conducted under WP4. In WP5, for career development and training, the MSCA fellow supervised 3 master students and 1 postdoc, served as a peer reviewer for academic journals in his field and secured 150,000€ in funding from the CNRS “prematuration program” to conduct (as a PI) the technologic development of an innovative 3D organoid culture system crucial for the development of WP3 focused on CRC patient-derived organoids study and biobanking. Last but not least he obtained a permanent research position at the French National Centre for Scientific Research (CNRS). In WP6, the fellow delivered 1 international conference presentation, 1 published article in peer review journals (where FUNTRICAN was mentioned), 1 pending patent (#FR2013109), 1 video, 1 science fair organization and 2 seminars for charity events.
Results of this MSCA are reported in a forthcoming paper related to the technology development. The data collected during this MSCA will also feed at least two additional research publications in the next two years.
Impact from the MSCA on the career development of the fellow are beyond expectation as he obtained a permanent research position in a famous french research institute. Before obtaining the MSCA fellowship, he wished to establish his own research program centered on the study of CSCs plasticity; more specifically, discovering and characterizing novel targets within the pathways that enhance the ability of CSCs to continue to self-renew, maintain pluripotency and thereby enable tumor relapse. Indeed, his research group is now actively analyzing the importance of complex interactions between signaling pathways in the intestinal stem cells.
With an overall failure rate in drug development of over 96%, including a 90% failure rate during clinical development there is an urgent need to establish more effective and stable preclinical tumor drug screening models to faithfully recapitulate the morphological and molecular characteristics of various human tumors. Tumor organoids could help in that way since they retained the genetic information of tumor tissue during long-term passages. However, since clonal drift inevitably occurred within these cultures, we need to improve culture standardization to guarantee (1) the success rate of tumor drug screening in clinical trials but also (2) the benefit for finding the most effective treatment for cancer patients. Therefore, the technology developed in FUNTRICAN project will facilitate studies on CRC tumor organoid cultures, but the methodology used is likely to impact also knowledge on tumoroid culture from other organs.
During the MSCA fellowship, he developed competences with many different research technics related to the organoid cell culture technology and manage to improve it drastically. From there, he developed an innovating 3D organoid culture system (patent pending #FR2013109) making him very competitive in the field and allowing him to develop a strong and interesting network of international scientists and industrial partners but also improved his communicating skills by sharing the results from the FUNTRICAN research program to a broad public.