Principles and Current Strategies for Targeting Autophagy for Cancer Treatment

By R. Amaravadi, Jennifer Lippincott-Schwartz, Xiao-Ming Yin, W. Weiss, N. Takebe, William C. Timmer, Robert S. DiPaola, Michael Lotze, E. White. Clinical Cancer Research, 2011

897 citations recorded by the source corpus.

Autophagy is an evolutionarily conserved, intracellular self-defense mechanism in which organelles and proteins are sequestered into autophagic vesicles that are subsequently degraded through fusion with lysosomes. Cells, thereby, prevent the toxic accumulation of damaged or unnecessary components, but also recycle these components to sustain metabolic homoeostasis. Heightened autophagy is a mechanism of resistance for cancer cells faced with metabolic and therapeutic stress, revealing opportunities for exploitation as a therapeutic target in cancer. We summarize recent developments in the field of autophagy and cancer and build upon the results presented at the Cancer Therapy Evaluation Program (CTEP) Early Drug Development meeting in March 2010. Herein, we describe our current understanding of the core components of the autophagy machinery and the functional relevance of autophagy within the tumor microenvironment, and we outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy. Finally, we describe ongoing clinical trials involving HCQ as a first generation autophagy inhibitor, as well as strategies for the development of novel, more potent, and specific inhibitors of autophagy. Clin Cancer Res; 17(4); 654–66. ©2011 AACR.

Subfields: Cell Biology, Epidemiology, Geriatrics and Gerontology

View Paper: https://www.semanticscholar.org/paper/ada1ef2c7291a7ea8f8a2f3c7c0f71e3bb377434

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Citations in the corpus

Targeting autophagy in cancer (2018, background): “Dysregulated autophagy has been implicated in several diseases, including neurodegenerative diseases,(3) cardiomyopathy,(4) infectious disease,(5) type II diabetes,(6) fatty liver,(7) and cancer.(8) Another way autophagy is categorized is into nonselective and selective autophagy.”
Autophagy and Tumor Metabolism (2017, background): “These findings have been extended to show that, in many cases, autophagy can promote survival during the stress of therapies (chemotherapy, radiotherapy, and targeted agents) and thus promotes therapeutic resistance (Amaravadi et al., 2011; Rebecca and Amaravadi, 2016; Thorburn et al., 2014).”
Autophagy: Renovation of Cells and Tissues (2011, background): “After these basic studies were published, >20 clinical trials of autophagy-inhibiting drugs (i.e., hydroxychloroquine and chloroquine) were initiated (http://clinicaltrials.gov/ct2/results?term=autophagy) (Amaravadi et al., 2011).”
Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment (2013, background): “It is consensus that the outcomes of autophagy activation are highly depended on the tumor types and treatment characteristic.(119,120)”
The dynamic nature of autophagy in cancer. (2011, background): “Subsequently, a series of studies have shown synergy of autophagy inhibition with a variety of cytotoxic, targeted agents and radiotherapy (Amaravadi et al. 2007, 2011; Carew et al. 2007; Apel et al. 2008; Degtyarev et al. 2008).”