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AACR 2022 | Combined inhibition of PARP and VEGF in gastric cancer

Michael Cecchini, Yale School of Medicine, New Haven, CT, explains the rationale behind combining vascular endothelial growth factor inhibitors (VEGFi) and poly (ADP-ribose) polymerase inhibitors (PARPi) as late-line treatment for gastric cancer (GC). PARP and VEGFR-2 signaling mediate angiogenesis and can contribute to the pathogenesis and progression of GC. Ramucirumab is a monoclonal antibody against VEGFR-2 and is an FDA approved second-line treatment for gastric cancer. Preclinical work has shown that hypoxia, which can be driven using VEGF directed agents such as ramucirumab, creates a stage of homologous recombination deficiency (HRD) phenotype that may be sensitized by using PARP inhibitor. This interview took place at the American Association for Cancer Research Annual Meeting 2022 in New Orleans, LA.