Chapters authored
Autophagy in Multidrug-Resistant Cancers
Multidrug resistance (MDR) in cancers is the major challenge in cancer therapy, thus the development of sensitizing agents or small molecules with new mechanisms of action to kill the resistant cancers is highly desired. Autophagy is a cellular process responsible for the turnover of misfolded proteins or damaged organelles and recycling of nutrients to maintain cellular homeostasis. Recently, autophagy has been shown to regulate MDR in cancers. In this chapter, both intrinsic and acquired drug resistance affecting the efficiency of chemotherapy, and the MDR mechanisms including nonclassical MDR phenotype and classical transport-based MDR phenotype were discussed. In addition, the development of apoptosis-resistant cancer by the deregulation of apoptotic gene machinery, such as BCL-2, BAX, BAK, and TRAILR, was also covered. We then further discussed the controversial role of autophagy by illustrating how induction of autophagy could work as a tumor suppressor or promote tumor survival. The modulation of MDR in cancer by either induction or inhibition of autophagy was also discussed. We have further summarized the current compounds or drugs for modulating MDR cancers and how autophagy modulators could circumvent the MDR phenotypes in cancers. Finally, the new mechanisms participating in MDR phenotypes were proposed for future MDR drugs discovery.
Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology