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Review
. 2011 Jan 15;11(2):157-68.
doi: 10.4161/cbt.11.2.14622. Epub 2011 Jan 15.

Autophagy as a therapeutic target in cancer

Ning Chen  1 , Vassiliki Karantza
Affiliations
Review

Autophagy as a therapeutic target in cancer

Ning Chen et al. Cancer Biol Ther. .

Abstract

Autophagy is a self-catabolic process that maintains intracellular homeostasis and prolongs cell survival under stress via lysosomal degradation of cytoplasmic constituents and recycling of amino acids and energy. Autophagy is intricately involved in many aspects of human health and disease, including cancer. Autophagy is a double-edged sword in tumorigenesis, acting both as a tumor suppressor and a protector of cancer cell survival, and elucidation of its exact role at different stages of cancer progression and in treatment responsiveness is a complex and challenging task. Better understanding of autophagy regulation and its impact on treatment outcome will potentially allow us to identify novel therapeutic targets in cancer. In this review, we summarize current knowledge on the regulation and dual function of autophagy in tumorigenesis, as well as ongoing efforts in modulating autophagy for cancer treatment and prevention. This is a very exciting and highly promising area of cancer research, as pharmacologic modulation of autophagy appears to augment the efficacy of currently available anticancer regimens and opens the way to the development of new combinatorial therapeutic strategies that will hopefully contribute to cancer eradication.

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Figures

Figure 1
Figure 1
Autophagy regulation. Growth factor signaling activates the PI3K/AKT/mTOR axis resulting in autophagy inhibition. In contrast, class III PI3K activates autophagy. Low cellular energy levels with increased AMP/ATP ratio activate the LKB1-AMPK-mTOR pathway to also upregulate autophagy. Furthermore, increased calcium ion levels induce autophagy by two mechanisms, i.e., the Ca2+-CaMKKβ-AMPK pathway and direct Ca2+-induced ER stress. p53 exhibits complex autophagy regulation, as nuclear p53 activated by genotoxic or oncogenic stress positively regulates autophagy by inhibiting mTOR in an activated AMPK- and TSC1/TSC2-dependent manner, whereas cytoplasmic p53 can suppress autophagy.
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