Key significance of an overachieving Epidermal Growth Factor Receptor (EGFR)-signaling in cancer aggressiveness and poor prognosis is well recognized. In accordance, EGFR is either amplified or mutated in majority of the cancers of epithelial origin, and therefore has been recognized as a principal target for anticancer therapy. However, despite initial clinical efficacy of the anti-EGFR therapy in cancer treatment, long-term attempt to mute the cancer boosting effects of EGFR-dependent signaling meets resistance in cancer cells. Notably, effects of EGFR activation are pleotropic. Also, under conditions of anti-EGFR therapy in cancer cells, feedback activation of the pro-survival signaling by activation of other growth factor receptors can occur. However, a critical role of autophagy in the resistance against anti-EGFR therapy is fast emerging. Interestingly, EGFR regulates autophagy in a context-dependent manner. Furthermore, EGFR deregulated tumors demonstrate differential dependence upon autophagy for their survival and growth. Also, inhibiting EGFR-signaling promotes autophagy. These intriguing considerations are complicated further by findings that EGFR regulates autophagy in kinase-dependent or independent manner. Thus, for effective clinical cancer treatment using anti-EGFR regimen, it is critical that we understand molecular details of the nexus between the EGFR-signaling and autophagy.
Keywords: Autophagy; Carcinogenesis; EGFR; Metabolic stress; Treatment resistance.