TY - JOUR
T1 - Targeting the EGFR signaling pathway in cancer therapy
T2 - What’s new in 2023?
AU - Halder, Sushanta
AU - Basu, Soumi
AU - Lall, Shobhit P.
AU - Ganti, Apar K.
AU - Batra, Surinder K.
AU - Seshacharyulu, Parthasarathy
N1 - Funding Information:
Authors in this manuscript was funded by the following grants from the National Institutes of Health/National Cancer Institute (NIH/NCI) Grants P01 CA217798 (SK Batra), U01 CA185148 (SK Batra), Department of Defense Award W81×WH-18-1-0308 (SK Batra), US Department of Veterans Affairs (I01 B×004676), and UNMC-Fred and Pamela Buffett Cancer Center Pilot grant CA036727 (P Seshacharyulu). We would like to thank the Mipanda data portal for the EGFR family member expression analysis in various cancers and data visualization. Cartoon images were created using BioRender.com
Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Introduction: Epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, and mutated in multiple cancers. In normal cell physiology, EGFR signaling controls cellular differentiation, proliferation, growth, and survival. During tumorigenesis, mutations in EGFR lead to increased kinase activity supporting survival, uncontrolled proliferation, and migratory functions of cancer cells. Molecular agents targeting the EGFR pathway have been discovered, and their efficacy has been demonstrated in clinical trials. To date, 14 EGFR-targeted agents have been approved for cancer treatments. Areas covered: This review describes the newly identified pathways in EGFR signaling, the evolution of novel EGFR-acquired and innate resistance mechanisms, mutations, and adverse side effects of EGFR signaling inhibitors. Subsequently, the latest EGFR/panEGFR inhibitors in preclinical and clinical studies have been summarized. Finally, the consequences of combining immune checkpoint inhibitors and EGFR inhibitors have also been discussed. Expert opinion: As new mutations are threatened against EGFR-tyrosine kinase inhibitors (TKIs), we suggest the development of new compounds targeting specific mutations without inducing new mutations. We discuss potential future research on developing EGFR-TKIs specific for exact allosteric sites to overcome acquired resistance and reduce adverse events. The rising trend of EGFR inhibitors in the pharma market and their economic impact on real-world clinical practice are discussed.
AB - Introduction: Epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, and mutated in multiple cancers. In normal cell physiology, EGFR signaling controls cellular differentiation, proliferation, growth, and survival. During tumorigenesis, mutations in EGFR lead to increased kinase activity supporting survival, uncontrolled proliferation, and migratory functions of cancer cells. Molecular agents targeting the EGFR pathway have been discovered, and their efficacy has been demonstrated in clinical trials. To date, 14 EGFR-targeted agents have been approved for cancer treatments. Areas covered: This review describes the newly identified pathways in EGFR signaling, the evolution of novel EGFR-acquired and innate resistance mechanisms, mutations, and adverse side effects of EGFR signaling inhibitors. Subsequently, the latest EGFR/panEGFR inhibitors in preclinical and clinical studies have been summarized. Finally, the consequences of combining immune checkpoint inhibitors and EGFR inhibitors have also been discussed. Expert opinion: As new mutations are threatened against EGFR-tyrosine kinase inhibitors (TKIs), we suggest the development of new compounds targeting specific mutations without inducing new mutations. We discuss potential future research on developing EGFR-TKIs specific for exact allosteric sites to overcome acquired resistance and reduce adverse events. The rising trend of EGFR inhibitors in the pharma market and their economic impact on real-world clinical practice are discussed.
KW - Cancer Therapy
KW - Dacomitinib
KW - EGFR
KW - EGFR mutations
KW - EGFR signalling
KW - Osimertinib
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85161408702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85161408702&partnerID=8YFLogxK
U2 - 10.1080/14728222.2023.2218613
DO - 10.1080/14728222.2023.2218613
M3 - Review article
C2 - 37243489
AN - SCOPUS:85161408702
SN - 1472-8222
VL - 27
SP - 305
EP - 324
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 4-5
ER -