Tumor growth fueled by spurious senescence phenotypes
Michalis Mastri1, John M L Ebos1,2
1Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Molecular & Cellular Oncology
|May 28, 2019
Abstract:
Cancer treatments can induce a form of senescence that halts cellular division while allowing continued secretion of tumor-promoting proteins. We recently found that antiangiogenic treatment resistance can lead to a transient hijacking of the senescence-controlled secretory machinery that, when therapeutically targeted during treatment cessation, can blunt rebound tumor growth.
Insights
Cancer treatments can cause senescence, halting cell division but promoting tumor growth via secreted proteins. Targeting this senescence-associated secretory phenotype during treatment breaks can reduce tumor regrowth.
Area of Science:
- Oncology
- Cellular Biology
- Cancer Therapeutics
Background:
- Cancer treatments can induce cellular senescence, a state of irreversible cell cycle arrest.
- Senescence can paradoxically promote tumor growth through the secretion of pro-tumorigenic factors, known as the senescence-associated secretory phenotype (SASP).
- Resistance to antiangiogenic therapies can involve the senescence-associated secretory phenotype.
Purpose of the Study:
- To investigate the role of the senescence-associated secretory phenotype in tumor rebound after antiangiogenic therapy cessation.
- To determine if therapeutic targeting of the senescence-associated secretory phenotype during treatment breaks can prevent tumor regrowth.
Main Methods:
- Utilized models of antiangiogenic treatment resistance in cancer.
- Analyzed the senescence-associated secretory phenotype during and after treatment cessation.
- Investigated therapeutic targeting of the senescence-associated secretory phenotype during treatment breaks.
Main Results:
- Confirmed that antiangiogenic treatment resistance is associated with a transient hijacking of the senescence-controlled secretory machinery.
- Demonstrated that therapeutic targeting of this machinery during treatment cessation blunts rebound tumor growth.
- Identified a window of vulnerability during treatment cessation for targeting senescence-associated secretory phenotype.
Conclusions:
- The senescence-associated secretory phenotype plays a critical role in mediating tumor rebound after antiangiogenic therapy.
- Targeting the senescence-associated secretory phenotype during treatment cessation represents a promising strategy to improve cancer treatment outcomes.
- This approach offers a novel therapeutic avenue for overcoming treatment resistance and preventing tumor recurrence.
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