Overview of the multifaceted resistances toward EGFR-TKIs and new chemotherapeutic strategies in non-small cell lung cancer
Document Type
Article
Publication Date
11-1-2022
Abstract
The role of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) has been vastly studied over the last decade. This has led to the rapid development of many generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, patients treated with third-generation TKIs (osimertinib, avitinib and rociletinib) targeting the EGFR T790M mutation have shown emerging resistances and relapses. Therefore, further molecular understanding of NSCLC mutations, bypass signalling, tumour microenvironment and the existence of cancer stem cells to overcome such resistances is warranted. This will pave the way for designing novel and effective chemotherapies to improve patients' overall survival. In this review, we provide an overview of the multifaceted mechanisms of resistance towards EGFR-TKIs, as well as the challenges and perspectives that should be addressed in strategising chemotherapeutic treatments to overcome the ever-evolving and adaptive nature of NSCLC.
Keywords
Lung cancer, NSCLC, EGFR-TKI, Cancer stem cells, Natural products
Divisions
fac_med
Funders
Ministry of Education, Malaysia [FRGS/1/2019/SKK09/UM/02/1],Universiti Malaya [RP035-17AFR]
Publication Title
Biochemical Pharmacology
Volume
205
Publisher
Elsevier
Publisher Location
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND