Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2011 Feb 15;17(4):654-66. doi: 10.1158/1078-0432.CCR-10-2634.

Principles and current strategies for targeting autophagy for cancer treatment.

Author information

  • 1Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Ravi.Amaravadi@uphs.upenn.edu

Abstract

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.

©2011 AACR.

PMID:
21325294
[PubMed - indexed for MEDLINE]
PMCID:
PMC3075808
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk