Autophagy signals orchestrate chemoresistance of gynecological cancers

Abstract

Gynecological cancers are characterized by a high mortality rate when chemoresistance develops. Autophagy collaborates with apoptosis and participates in homeostasis of chemoresistance. Recent findings supported that crosstalk of necrotic, apoptotic and autophagic factors, and chemotherapy-driven hypoxia, oxidative stress and ER stress play critical roles in chemoresistance in gynecological cancers. Meanwhile, current studies have shown that autophagy could be regulated by and cooperate with metabolic regulator, survival factors, stemness factors and specific post-translation modification in chemoresistant tumor cells. Meanwhile, non-coding RNA and autophagy crosstalk also contribute to the chemoresistance. Until now, analysis of individual autophagy factors towards the clinical significance and chemoresistance in gynecological cancer is still lacking. We suggest comprehensive integrated analysis of cellular homeostasis and tumor microenvironment to clarify the role of autophagy and the associated factors in cancer progression and chemoresistance. Panel screening of pan-autophagic factors will pioneer the development of risk models for predicting efficacy of chemotherapy and guidelines for systematic treatment and precision medicine.

Keywords: Autophagy; Chemoresistance; Epigenetic control; Metabolic regulation; Recurrence monitoring; Stemness properties.