Abstract:
Autophagy is a naturally occurring programed cellular catabolic process stimulated by cellular stress for energy homeostasis
maintenance and elimination of harmful substances. It mostly works as pro-survival mechanism but on the other hand deregulation
of autophagy has been linked to non-apoptotic cell death known as “type II programed cell death.” Emerging evidences
indicate that EGFR (epidermal growth factor receptor)-mediated RAS/RAF/MEK/ERK signaling pathway plays a critical role in
the induction of autophagy in various tumors. It has further been established that this signaling pathway is also involved in
several other anti-proliferative events such as apoptosis and senescence. However, the signaling pathway activity and effects
are highly dependent on the cell type and the stimulus. It is currently being evident that autophagy induction by RAS/RAF/
MEK/ERK pathway through small molecules may be a potential therapeutic strategy for cancer. However, to our best knowledge,
the role of EGFR-mediated RAS/RAF/MEK/ERK signaling pathway in autophagy-mediated cell death and survival have not
previously been reviewed. In this review, we discuss the current state of knowledge on how RAS/RAF/MEK/ERK signaling pathway
regulates autophagy and the role of this EGFR-mediated autophagy in diseases. We further examine the cross-talk
between this EGFR-mediated autophagy and apoptosis as well as how this process is currently being utilized for cancer treatment
and suggest promoting autophagy-related cell death by small molecules may be exploited to design better therapeutic
strategies for early stage and locally advanced tumors
