Untangling knots between autophagic targets and candidate drugs, in cancer therapy

Abstract

Autophagy is an evolutionarily conserved lysosomal mechanism implicated in a wide variety of pathological processes, such as cancer. Autophagy can be regulated by a limited number of autophagy-related genes (Atgs) such as oncogenic Bcl-2/Bcl-XL , mTORC1, Akt and PI3KCI, and tumour suppressive proteins PI3KCIII, Beclin-1, Bif-1, p53, DAPKs, PTEN and UVRAG, which play their crucial roles in regulating autophagy-related cancer. As autophagy has a dual role in cancer cells, with tumour-promoting and tumour-suppressing properties, it has become an attractive target for a series of emerging small molecule drugs. In this review, we reveal new discoveries of related small molecules or chemical compounds that can regulate autophagic pathways and lead to pro-death or pro-survival autophagy, in different types of cancer. We discuss the knots between autophagic targets and candidate drugs, in the hope of shedding new light on exploiting new anti-tumour small molecule drugs for future cancer therapy.