EPHA3 (3p11.2) encodes a transmembrane protein with 983 amino acids that is widely expressed during embryonic development, overexpressed in the nervous system and heart, and exhibits lower expression in the brain, lung, bladder, prostate, and colon. Studies have shown that EPHA3 exhibits abnormal expression in a variety of cancers, such as colorectal cancer, glioblastoma multiforme, melanoma, and hepatocellular cancer. A recent collaborative study of 188 lung adenocarcinomas by Ding et al. revealed that EPHA3 is the Eph receptor found to be most frequently mutated in lung cancer, with 19 missense mutations identified so far and a mutation rate of 6 %. Zhuang et al. further investigated the EPHA3 mutations and identified an EPHA3 mutation-associated gene signature in lung cancer that was associated with poor patient survival. Moreover, EPHA3 gene copy numbers and/or expression levels were decreased in tumors from large cohorts of patients with lung cancer. Re-expression of wild-type EPHA3 in human lung cancer lines increased apoptosis by suppression of AKT activation in vitro and inhibited the growth of tumor xenografts . Although Ross et al. detected 98 SCLC samples by next-generation sequencing and found amplifications of EPHA3 genes in three cases of SCLC, EPHA3 associated with SCLC has rarely been published previously and little is known about the role of EPHA3 genes in chemoresistance.
Peng J, Wang Q, Liu H, Ye M, Wu X, Guo L. EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway. Tumour Biology. 2016;37(9):11959-11971.