Targeting R2TP/TTT/WAC/mTOR complex in ovarian cancer.

Ovarian Cancer (OC) is the most lethal gynecological tumor and has an especially high impact in Europe. 70% of patients develop an advanced stage due to the lack of early diagnosis tools and chemotherapy resistance. Therefore, a better understanding of altered molecular mechanisms driving OC progression is needed.

Preliminary data from the host lab suggest that a complex formed by R2TP/TTT/WAC upon glucose and glutamine depletion, impairs mTOR activation.

Moreover, the components of this complex are co-expressed in OC, a disease influenced by mTOR signaling and metabolic reprogramming.

Thus, our hypothesis is that WAC regulates an mTOR activation pathway that influences OC progression and response to chemotherapy and that targeting this complex is a potential therapeutic prospect for the treatment of OC.

In particular, we propose to (i) establish the mechanism and role of the R2TP/TTT/WAC/mTOR complex in OC and (ii) to identify new therapeutic strategies targeting this complex for the treatment of OC.We have envisioned this project as a diverse node of cancer signaling and protein experts, with a predicted outcome highly transferable to society.

The translational character of this proposal, from molecular mechanism to therapeutics, relies on the integration of an interdisciplinary team formed by the host group proficiency in Structural Biology and my expertise in Molecular Biology and Drug Discovery, together with scientific experts on Experimental Therapeutics and Bioinformatics from the host institution and collaborators.

Importantly, I will have the opportunity to develop new professional skills by both scientific exchanges and specific courses and to participate in dissemination activities to translate our findings to the scientific community and society.

Thus, the MSCA fellowship will allow me to develop unique technical and transferable skills, to help me progress in my career developmental plan and establish myself as a leader in cancer research in Europe.