Tumors Responsive to Autophagy-Inhibition: Identification and Biomarkers

Simple Summary Although the principle of personalized medicine has been the focus of attention, many cancer therapies are still based on a one-size-fits-all approach. The same holds true for targeting cancer cell survival mechanism that allows cancer cells to recycle their constituents (autophagy). In the past several indicators of elevated dependence of cancer cells on autophagy have been described. Addition of autophagy-inhibiting agents could be beneficial in treatment of these tumors. The biomarkers and mechanisms that lead to elevated dependence on autophagy are reviewed in the current manuscript. Recent advances in cancer treatment modalities reveal the limitations of the prevalent "one-size-fits-all" therapies and emphasize the necessity to develop personalized approaches. In this perspective, identification of predictive biomarkers and intrinsic vulnerabilities are an important advancement for further therapeutic strategies. Autophagy is an important lysosomal degradation and recycling pathway that provides energy and macromolecular precursors to maintain cellular homeostasis. Although all cells require autophagy, several genetic and/or cellular changes elevate the dependence of cancer cells on autophagy for their survival and indicates that autophagy inhibition in these tumors could provide a favorable addition to current therapies. In this context, we review the current literature on tumor (sub)types with elevated dependence on autophagy for their survival and highlight an exploitable vulnerability. We provide an inventory of microenvironmental factors, genetic alterations and therapies that may be exploited with autophagy-targeted approaches to improve efficacy of conventional anti-tumor therapies.