1. Dual EGFR-VEGF Pathway Inhibition: A Promising Strategy for Patients With EGFR-Mutant NSCLC
- Author
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John V. Heymach, Terafumi Kato, Edward B. Garon, Carla Visseren-Grul, Kazuhiko Nakagawa, Jonathan H. Goldman, Monique B. Nilsson, Martin Reck, Bente Frimodt-Moller, L. Arés, Xiuning Le, and Katharina Wolff
- Subjects
Vascular Endothelial Growth Factor A ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Bevacizumab ,Angiogenesis ,Mutant ,medicine.disease_cause ,Ramucirumab ,03 medical and health sciences ,0302 clinical medicine ,Mediator ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Protein Kinase Inhibitors ,business.industry ,respiratory tract diseases ,ErbB Receptors ,Clinical trial ,030104 developmental biology ,Oncology ,Vegf pathway ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,business ,Carcinogenesis ,medicine.drug - Abstract
The VEGF pathway has been recognized as a key mediator of angiogenesis to support tumorigenesis. Multiple therapeutic agents targeting VEGF and VEGF receptors have been developed and approved for use in NSCLCs. Preclinical studies have found that the VEGF and EGFR pathways share common downstream signaling, and these pathways can function exclusively of one another during oncogenesis. In EGFR-mutant NSCLCs, up-regulated EGFR signaling increases VEGF through hypoxia-independent mechanisms, and elevated VEGF, in turn, contributes to the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs). In clinical trials, the addition of anti-VEGF therapy to EGFR TKIs considerably improved clinical outcomes. In recently reported large randomized studies, the addition of bevacizumab or ramucirumab to EGFR TKIs substantially improved progression-free survival in patients with TKI-naive EGFR-mutant NSCLC. This article reviews the preclinical and clinical data supporting dual inhibition of EGFR and VEGF in EGFR-mutant NSCLC as a way to improve patient outcomes.
- Published
- 2021