Therapy-induced senescence in prostate cancer: mechanisms, therapeutic strategies, and clinical implications

Area of Science:

• Oncology
• Cell Biology
• Cancer Therapeutics

Background:

• Prostate cancer (PCa) is a leading cause of male cancer mortality, with advanced stages posing significant challenges.
• Therapy resistance and disease progression are major hurdles in PCa treatment.
• Therapy-induced senescence (TIS) is an underappreciated mechanism influencing treatment response in PCa.

Purpose of the Study:

• To review the molecular mechanisms of senescence in PCa.
• To explore therapeutic strategies that induce senescence.
• To discuss the dual role of TIS in PCa progression and treatment resistance.

Main Methods:

• Review of molecular mechanisms of senescence.
• Analysis of therapeutic strategies inducing senescence.
• Exploration of senescence-associated secretory phenotype (SASP) in PCa.
• Discussion of senolytics and senomorphics.

Main Results:

• TIS is induced by various PCa treatments (chemotherapy, radiotherapy, hormonal, targeted agents).
• TIS exhibits both tumor-suppressive and tumor-promoting effects via SASP.
• Persistent senescent PCa cells contribute to treatment resistance and disease progression.

Conclusions:

• Senotherapy, combining senescence induction with targeting senescent cells (senolytics/senomorphics), is a promising strategy for PCa.
• Mitigating adverse effects of persistent senescent cells is crucial for improving PCa treatment outcomes.
• Further research and clinical trials are needed to integrate senotherapy into PCa management.