Autophagy and Multidrug Resistance in Cancer

The primary tenets of cancer treatment are the induction of cellular apoptosis and the suppression of cell viability. The issue of chemotherapeutic resistance is a significant challenge in the field of oncology, which further impedes the efficacy of anticancer medications. Drug resistance is influenced by a multitude of variables, including host-related elements, as well as unique genetic or epigenetic modifications inside the cancer cells, among other contributing factors. While there is a considerable understanding of the several processes via which cancer cells develop resistance to anticancer medications inside the microenvironment, there is still a need to determine strategies to overcome this resistance to enhance the effectiveness of anticancer treatments. Factors like protein-protein interactions, non-coding RNA, tumor microenvironment, gene mutations, and autophagy may account for developing multidrug resistance of which autophagy is a vital cellular mechanism involved in the degradation and recycling of intracellular components. It is often used in the management of both sensitive and multidrug-resistant cancers, and its impact might vary depending on the specific characteristics of the tumor cells and tissues. Autophagy can be viewed as a dual-edged sword in the context of multidrug-resistant (MDR) malignancies. On the one hand, it contributes to the progression of MDR by aiding in the establishment of resistance mechanisms and safeguarding cancer cells from the cytotoxic effects of chemotherapeutic agents. On the other hand, autophagy may also induce cell death in MDR cancer cells that lack functional apoptotic pathways. This chapter introduces us to the concept of MDR and its multifactorial nature. It then sheds light on the autophagy process with a summary of its regulation via developing mechanisms, the impact of targeting autophagy on drug resistance, and novel treatment strategies aimed at addressing tumor drug resistance by modulating autophagy-related pathways.