Empowered Patient Podcast

Focusing on Synthetic Lethality and Targeting the DNA Damage Response Pathway to Kill Cancer Cells with Oren Gilad Aprea Therapeutics

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Oren Gilad, President and CEO of Aprea Therapeutics, focused on the DNA damage response pathway, specifically targeting the ATR protein. ATR is a master regulator of DNA replication and is hyperactive in cancer cells, making it a potential Achilles heel for cancer therapy. By inhibiting ATR, cancer cells can be selectively targeted, while normal cells can tolerate lower levels of ATR activity. Synthetic lethality is applied when two genetic mutations are combined, leading to cell death, specifically in cancer cells. Aprea is conducting clinical trials for their targeted treatments, focusing on solid tumors with defined genetic mutations. Oren explains, "DDR, the DNA damage response pathway, is the broader terminology for the regulation of DNA synthesis. In order for cancer to grow, cells have to duplicate. In order for them to duplicate, they have to replicate their DNA. So what happens is that cancer cells get into this DNA replication phase very early and prematurely, causing a single-strand DNA to be expos