Natural Compounds and their Nano-formulations in Combating Autophagy-mediated Drug Resistance in Human Cancers.

Abstract

Autophagy is a crucial mechanism that maintains cellular homeostasis and has emerged as a pivotal factor in cancer progression and drug resistance. Despite autophagic regulations being a complex process, convincing evidence shows that PI3K-Akt-mTOR, LKB1-AMPK-mTOR, and p53 pathways are the primary upstream regulators of the autophagy process. Currently, there is an immense amount of evidence demonstrating that autophagy plays a crucial role in cancer. It is worth noting that autophagy increases cancer cells' resistance to chemotherapy and anticancerous drugs. According to studies, cancer cells employ autophagy to evade the cytotoxic impacts of several anticancer drugs, resulting in autophagy-mediated drug resistance. This resistance brings a significant challenge to cancer management, emphasising the need for improved therapeutic strategies to overcome this obstacle and enhance the efficacy of cancer treatments. Therefore, this review gathers current data and findings to understand the intricate mechanism between autophagymediated drug resistance and cancer progression. Moreover, this study highlights the intriguing role of natural compounds and nano-formulations in combating autophagy-mediated drug resistance in various carcinomas, presenting a promising avenue for the effective management of cancer treatment.