Autophagy as a target for hematological malignancy therapy

Abstract

Autophagy is an essential metabolic pathway by which the intracellular unwanted materials are digested within lysosomes for cellular homeostasis. It provides energy and building blocks upon starvation or other stresses. Autophagy even contributes to cell death especially under apoptosis incompetent conditions depending on the cellular contexts. Dysfunction of autophagy involves in the initiation and progression of multiple diseases and their treatments. But its principles and clinical applications have not been fully elucidated yet. Basal autophagy may serve as a tumor suppressive mechanism during tumorigenesis; nevertheless, excessive autophagy even works as a pro-survival pathway in already established cancers. Recently, mounting evidence highlighted its key roles in the genesis and therapy of various hematological malignancies. The combinations of autophagy inhibitors (such as chloroquine) with some first-line drugs, as well as novel autophagy-based manipulations, including Bcl-2 family regulation, caspase-dependent cleavage of ATG proteins and microRNA replacement are clinically or experimentally applied, representing promising approaches for their clinical treatments. This review is therefore to discuss the recent progress in autophagy machinery and its association with hematological malignancy therapy.

Keywords: AMPK; Autophagy; Bcl-2; Hematological malignancy; MicroRNA; PI3K.