Targeting the DNA damage response in cancer treatment

Speaker: Josep Forment, PhD & Paola Marco Casanova , PhD
Institution: Bioscience Department Director & Associate Director at AstraZeneca

Place: Jerónimo Forteza conference room, CIPF

Abstract: Genomic instability is one of the hallmarks of cancer as it allows generation of genetic diversity required for tumour development and plasticity. However, it also generates vulnerabilities that can be targeted by pharmacological inhibition of components of the so-called DNA damage response (DDR) pathway. In this talk, we will focus on the development of inhibitors of poly(ADP-ribose) polymerases (PARP) and of the apical DDR regulatory kinase ATR. We will discuss the concept of synthetic lethality and how we apply it to treat cancer, how this led to the approval of PARP inhibitors (PARPi) in the clinic, how we are exploring the use of these drugs in alternative cancer settings and our efforts to identify ways to overcome PARPi resistance. In addition, we will explain how translational analyses are key to identify the right patients and right doses for targeted therapies, and how we identified an alternative mechanism of action for ATR inhibitors that has led to promising clinical trial results in combination with immune therapy.

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