Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Abstract

Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

Inhibition of autophagy potentiates the cytotoxicity of the irreversible FGFR1-4 inhibitor FIIN-2 on lung adenocarcinoma

“…Autophagy is a conservative cellular catabolic process [ 21 ]. During metabolic stress, such as drug treatment, tumour cells can clear and recycle various damaged organelles (e.g., mitochondria) by initiating autophagy to protect tumour cells [ 38 ]. Mitochondrial damage leads to a decrease in MMP.…”

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

“…Chemotherapy remains the most effective first-line therapeutic approach for all stages of cancer and can effectively improve the clinical outcomes of patients in the short term. However, its long-term role in extending the OS of cancer patients is extremely restricted due to the emergence of drug resistance ( 43 ). Drug resistance is classified into single drug resistance and multidrug resistance (MDR).…”

Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment

“…At the same time, Genistein enhanced the sensitivity of sorafenib resistant HCC cells in vivo and in vitro ( 157 ); (b) crosstalk between autophagy and mitophagy. In the context of increased metabolic demands, mitophagy and autophagy may play key roles in inducing chemoresistance by regulating the adaptation of tumor cells to hypoxia, increasing oxidative stress and DNA damage, and providing nutrition and energy to tumor cells ( 158 ). B-cell lymphoma-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) and BNIP3-like protein X (NIX) are hypoxia-induced HIF-1α target genes that can bind LC3 and trigger the mitophagy response ( 159 ).…”