SYNTRAIN · Targeting SYNthetic lethal interactions for new cancer treatments TRAINing network

Targeting SYNthetic lethal interactions for new cancer treatments TRAINing network

Breast and ovarian cancer constitute serious health challenges in the EU, they are among the leading causes of death among women. There is a clear need to identify new improved breast and ovarian cancer therapeutic approaches. SYNTRAIN aims to innovate breast and ovarian cancer therapeutic options through new concepts originating in basic science settings within the laboratories of beneficiaries. The new concept was a multi-facetted synthetic lethal approach, which takes advantage of the inherent genetic instability of cancer cells. Most mutations acquired by cancer cells do not cause lethality, but the very same mutations may cause cell death when a second gene in a redundant pathway is inactivated. Thus, targeting a gene that is synthetic lethal together with a cancer-specific mutation will kill only cancer cells while sparing normal cells. Synthetic lethal approaches have been clinically pioneered by members of our consortium, by combining cancer-promoting mutations (e.g. in BRCA2) with inactivating combinations of DNA repair genes. We have used this approach as the scientific frame for our ETN consisting of 9 academic and 1 SME beneficiary as well as 4 partners. We aimed to identify synthetic lethal interactions and exploit them to innovate future breast and ovarian cancer treatments through compound screening and development. SYNTRAIN consists of world leading researchers with complementary knowledge in genome maintenance and stress response pathways, and a critical mass of expertise for providing an excellent training in screening methodologies, mechanistic investigations, and drug discovery. We offered a structured training program that exceeds the capacities of each individual member. We have now educated a future generation of cancer researchers with a high innovative capacity and skills that enhance their career prospects in both academia and industry. We have trained 15 young researchers in a structured, internationalized and intersectorial programme: i) in techniques preparing for a career in cancer research, ii) in complementary skills relevant for work in academia and the pharma industry and iii) to become creative and entrepreneurial, capable of bridging the gap between basic and applied research. SYNTRAIN offered and carried out a comprehensive cross-European training program for 15 ESRs, which included intersectoral involvement with secondments to academic laboratories and companies. In spite of COVID-19 challenges, all training events were executed and fellows advanced towards their PhD degrees. The project has also been highly successful at the scientific level. Multiple publications are published and many more are under preparation to disseminate the important findings. Briefly, SYNTRAIN research has led to the identification of new druggable targets and pathways. These targets have been carefully investigated to uncover their potential as drug targets. Furthermore, compound discovery and development has also been an important part of SYNTRAIN leading to patents and patent submissions to exploit our discoveries. We expect to harvest the fruits of the hard collaborative work in the coming years as the projects continue in the network laboratories.

Data: CORDIS, © European Union