Targeting Oncogene-Induced Autophagy: A New Approach in Cancer Therapy?

Abstract

Autophagy is a tightly controlled self-degradation process utilised by cells to sustain cellular homeostasis and to support cell survival in response to metabolic stress and starvation. Thus, autophagy plays a critical role in promoting cell integrity and maintaining proper function of cellular processes. Defects in autophagy, however, can have drastic implications in human health and diseases, including cancer. Described as a double-edged sword in the context of cancer, autophagy can act as both suppressor and facilitator of tumorigenesis. As such, defining the precise role of autophagy in a multistep event like cancer progression can be complex. Recent findings have implicated a role for components of the autophagy pathway in oncogene-mediated cell transformation, tumour growth, and survival. Notably, aggressive cancers driven by Ras oncoproteins rely on autophagy to sustain a reprogrammed mitochondrial metabolic signature and evade cell death. In this review, we summarize our current understanding of the role of oncogene-induced autophagy in cancer progression and discuss how modulators of autophagic responses can bring about therapeutic benefit and eradication of a subset of cancers that are addicted to this ancient recycling machinery.