Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect

Abstract

Autophagy is a conserved cellular process required to maintain homeostasis. The hallmark of autophagy is the formation of a phagophore that engulfs cytosolic materials for degradation and recycling to synthesize essential components. Basal autophagy is constitutively active under normal conditions and it could be further induced by physiological stimuli such as hypoxia, nutrient starvation, endoplasmic reticulum stress,energy depletion, hormonal stimulation and pharmacological treatment. In cancer, autophagy is highly context-specific depending on the cell type, tumour microenvironment, disease stage and external stimuli. Recently, the emerging role of autophagy as a double-edged sword in cancer has gained much attention. On one hand, autophagy suppresses malignant transformation by limiting the production of reactive oxygen species and DNA damage during tumour development. Subsequently, autophagy evolved to support the survival of cancer cells and promotes the tumourigenicity of cancer stem cells at established sites. Hence, autophagy is an attractive target for cancer therapeutics and researchers have been exploiting the use of autophagy modulators as adjuvant therapy. In this review, we present a summary of autophagy mechanism and controlling pathways, with emphasis on the dual-role of autophagy (double-edged sword) in cancer. This is followed by an overview of the autophagy modulation for cancer treatment and is concluded by a discussion on the current perspectives and future outlook of autophagy exploitation for precision medicine.

Cell Biology Meets Cell Metabolism: Energy Production Is Similar in Stem Cells and in Cancer Stem Cells in Brain and Bone Marrow

“…98 Autophagy protects cells during early steps of carcinogenesis, but once cancer cells are established, autophagy protects cancer cells against therapeutically induced cellular damage. 92,97,99 Abbreviations: HSCs, hematopoietic stem cells; NSCs, neural stem cells; HPCs, hematopoietic progenitor cells; NPCs, neural progenitor cells; GSCs, glioblastoma stem cells; LSCs, leukemic stem cells; FDA, Food and Drug Administration.…”

State of the Art on Toxicological Mechanisms of Metal and Metal Oxide Nanoparticles and Strategies to Reduce Toxicological Risks

“…This has been demonstrated with CTAB-coated Au-nanorods, which possessed higher toxicity than Au-nanorods coated with PSS and PDDAC [ 102 ]. This could be interesting for future biomedical applications since recently some researchers have focused on autophagy mechanism as a possible treatment for cancer [ 103 , 104 ].…”

The Role of Autophagy in the Progression and Treatment of Tumors

“…Owing to the context-driven role of autophagy in cancer, its systemic inhibition can give rise to variable effects on different organs or tissues. Therefore, the therapeutic focus of manipulating autophagy in the treatment of tumors has been mainly to augment, and/or lower the resistance to, other anticancer medicines [6,24,92,93]. During the advanced stages of cancer, chemoresistance becomes the main obstacle to successful treatment.…”