Heymach paper is out in pre-proof version, “Altered regulation of HIF-1a in naïve- and drug-resistant EGFR mutant NSCLC: implications for a VEGF-dependent phenotype”. Interesting discovery the authors made is that regulation of expression of VEGF is very different in tumors without and without EGFR mutations. To remind you, VEGF is a growth factor released by tumor cells to guide growth of blood vessels to the tumor and provide oxygen. In non-EGFR mutated tumors, expression of VEGF is regulated by hypoxia via transcription factor HIF-1a. However, in EGFR mutant NSCLC, EGFR signaling is the dominant regulator of HIF-1a and VEGF in a hypoxia-independent manner. The authors conclude that their data suggest that EGFR mutant NSCLC patients may receive greater benefit for VEGF blockade than patients with wild-type EGFR and supports the clinical testing and use of VEGF inhibitors in combination with EGFR TKIs.
They used mouse models of EGFR Ex20ins NSCLC treated with Bevacizumab (Avastin), antibody neutralizing VEGF, and Poziotinib. Look at PFS in one of the Figures:
Vehicle – 20 days
Bevacizumab – 40 days
Pozioinib – 41 days
Pozi+Bev – 125 days
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