EGFR targeted therapy resistance: current status, challenges, and future outlook
Lung cancer is the leading cause of cancer mortality worldwide. Recent progress has improved outcomes for many lung cancer patients. In particular, activating genetic alterations in the oncogenic driver genes such as the epidermal growth factor receptor (EGFR) are now successfully targeted with agents such as the EGFR tyrosine kinase inhibitor osimertinib. Despite progress, drug resistance remains a barrier to complete and long-term tumor responses. Indeed, most patients do not survive with EGFR mutant lung cancer as a chronic disease and instead succumb to the disease within a few years due to the emergence of resistance.
This volume focuses on the problem of drug resistance through the prism of EGFR mutant lung cancer. The sections focus on both on-target and off-target mechanisms of resistance to EGFR inhibitors in clinical use. There are discussions of inter- and intra-tumor heterogeneity that is a key challenge to further progress in transforming lung cancer into a chronic disease for all patients.
Solutions to the challenges of drug resistance are discussed. Improved molecular diagnostics and various therapeutic strategies tailored to the molecular biology of drug resistance in individual patients and patient subsets are explored.
This volume promises to enhance the understanding of continued research to further improve outcomes for EGFR mutant lung cancer patients through mechanism-based investigation and clinical trials.
Acknowledgments
Funding: This research project was conducted with support from the National Institutes of Health (R01CA231300, U54CA224081, R01CA204302, R01CA211052 and R01CA169338) and the Pew and Stewart Foundations to TGB.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease for the series “Mechanisms of Resistance to EGFR-targeted Therapy”. The article did not undergo external peer review.
Conflicts of Interest: The series “Mechanisms of Resistance to EGFR-targeted Therapy” was commissioned by the editorial office without any funding or sponsorship. TGB is an advisor to Novartis, Astrazeneca, Revolution Medicines, Array, Springworks, Strategia, Relay, Jazz, Rain and receives research funding from Novartis and Revolution Medicines and served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Journal of Thoracic Disease from Nov 2018 to Oct 2020.
Ethical Statement: The author has completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.04.08). The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
