The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment...

Area of Science:

• Oncology
• Cellular Biology
• Radiation Science

Background:

• Radiotherapy is a key cancer treatment, but ionizing radiation can induce cellular senescence in tumor and normal cells.
• Senescent cells arrest cell division but remain metabolically active, secreting factors that alter the tumor microenvironment (TME).

Purpose of the Study:

• To review the mechanisms linking radiation injury to senescence.
• To discuss the dual role of senescence in cancer treatment and its long-term consequences.
• To evaluate emerging therapeutic strategies targeting senescence.

Main Methods:

• Review of literature on radiation-induced senescence pathways.
• Analysis of the senescence-associated secretory phenotype (SASP) and its impact on the TME.
• Evaluation of senolytics, senomorphics, and immunotherapy for senescence modulation.

Main Results:

• Radiation induces senescence via DNA damage, oxidative stress, telomere dysfunction, and epigenetic changes.
• Early senescence can enhance immune surveillance, but persistent SASP promotes tumor recurrence, resistance, and normal tissue toxicity.
• Therapeutic strategies include senolytics, senomorphics, and immunotherapies to manage senescence.

Conclusions:

• Cellular senescence following radiotherapy has context-dependent effects, posing both benefits and risks.
• Targeting senescence pathways offers promising avenues for improving cancer therapy efficacy and reducing toxicity.
• Further research on biomarkers and safety profiles is crucial for clinical translation.