Chapters authored
Median Effect Dose and Combination Index Analysis of Cytotoxic Drugs Using Flow Cytometry
Part of the book: Flow Cytometry
Targeting Mitophagy in Combined Therapies of Haematological Malignancies
Mitophagy is a selective form of autophagy that eliminates mitochondria and is part of a larger network of mitochondrial quality control processes that respond to mitochondrial damage. Treatment of haematological malignancies often involves drugs that ultimately cause cell death by mitochondrial injury and initiation of apoptosis. Thus, mitophagy is a potential cause of resistance to anticancer drugs that target the mitochondria (mitocans). Since mitophagy is integrated to mitochondrial biogenesis, mitochondrial fission and fusion, the bioenergetics profile and metabolic reprogramming of tumour cells, the blockage of mitophagy may not be sufficient to overcome resistance. In addition, the mitochondrial unfolded protein response and the outer mitochondrial membrane-associated degradation have extensive crosstalk with mitophagy, and advanced forms of neoplasms will require targeting both systems. Proteasome inhibitors and vinca alkaloids target many of the critical steps involved in resistance to mitocans, while inducers of mitochondrial turnover (biogenesis and mitophagy) like valproic acid have a variable effect depending on metabolic reprograming and the activity of oxidative phosphorylation of tumour cells. Here we discuss the mechanisms of mitophagy and its associated mechanisms, and discuss its application to the rationale of targeted combined therapies of low- and high-grade B-cell neoplasms.
Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology