Introduction
Gastric cancer, death, tumours, hypoxia, toxicity, HRD, Hypoxia, adenocarcinoma, tumour-related, gastric cancer
GASTRIC CANCER, TUMOURS, HYPOXIA, HYPOXIA, ADENOCARCINOMA, GASTRIC CANCER
Gastric cancer remains one of the largest global causes of cancer-related death, and while the incidence has declined in the United States, the incidence of the lower oesophageal and gastroesophageal junction (GEJ) adenocarcinoma has increased dramatically over the past several decades in western countries [Ramucirumab is a monoclonal antibody against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2, ramucirumab prevents VEGF ligands from binding to VEGFR2 and ultimately impairs tumour-related angiogenesis. Substantial preclinical work has shown that hypoxia can induce homologous recombination deficiency (HRD) in tumours. Hypoxia reduces the expression of Genomic signatures suggest that up to 12% of gastric cancer has evidence of HRD at baseline [Given the supporting preclinical data that hypoxia sensitises tumours to PARP inhibitors, we proposed to evaluate the combination of a PARP inhibitor in combination with ramucirumab, an approved treatment targeting angiogenesis in metastatic gastric and GEJ adenocarcinoma. Due to non-overlapping toxicity profiles, we hypothesised that olaparib and ramucirumab would be well-tolerated and that ramucirumab would sensitise tumours to olaparib, thus enhancing overall response rates (ORR) compared to historical control of 3% with single-agent ramucirumab [