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Autophagy as a target for cancer therapy: new developments
Jennifer S Carew1, Kevin R Kelly, Steffan T Nawrocki
1The Department of Medicine and Institute for Drug Development, Cancer Therapy and Research Center at The University of Texas Health Science Center, San Antonio, TX, USA.
Abstract:
Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy.
Insights
Autophagy, a cellular recycling process, can suppress tumors but also aid cancer survival. Inhibiting autophagy enhances anticancer drug effectiveness, showing promise as a global cancer treatment strategy.
Area of Science:
- Cellular Biology
- Oncology
- Molecular Medicine
Background:
- Autophagy is a conserved lysosomal degradation pathway crucial for cellular homeostasis.
- While potentially tumor-suppressive, autophagy can also promote cancer cell survival under stress.
- Cancer cells exploit autophagy for nutrient and energy generation, contributing to drug resistance.
Purpose of the Study:
- To review anticancer agents that modulate autophagy.
- To discuss advancements in autophagy inhibition as a cancer treatment strategy.
- To highlight the role of autophagy in cancer drug resistance.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of anticancer agents affecting autophagy.
- Examination of autophagy inhibition as a therapeutic approach.
Main Results:
- Autophagy induction can promote cancer cell survival and drug resistance.
- Inhibition of autophagy potentiates the efficacy of various anticancer agents.
- Numerous clinical trials are investigating autophagy inhibition in cancer therapy.
Conclusions:
- Targeting autophagy represents a promising global strategy to enhance conventional cancer therapies.
- Autophagy inhibition may improve the effectiveness of standard-of-care treatments.
- Further research and clinical trials are essential to fully realize the therapeutic potential of autophagy modulation in oncology.
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