Therapy-induced senescence in breast cancer: an overview

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• Breast cancer outcomes have improved, yet drug resistance remains a significant challenge, leading to recurrence and metastasis.
• Drug therapy-induced senescence (TIS) is a key mechanism of acquired resistance, characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP).
• Various anticancer therapies can induce TIS by causing genotoxic stress, pathway hyperactivation, or oxidative stress.

Purpose of the Study:

• To review the characteristics of TIS in breast cancer.
• To detail the phenotypic changes associated with TIS induction.
• To discuss strategies for targeting senescent cells to prevent tumor recurrence.

Main Methods:

• Literature review of studies on drug therapy-induced senescence in breast cancer.
• Analysis of phenotypic changes accompanying TIS.
• Exploration of therapeutic strategies targeting senescent cells.

Main Results:

• TIS, induced by anticancer drugs, leads to cell cycle arrest and SASP.
• While TIS can be anti-tumorigenic short-term, it becomes pro-tumorigenic long-term by creating a pro-inflammatory, immunosuppressive microenvironment.
• The SASP promotes angiogenesis and epithelial-mesenchymal transition, potentially driving metastasis.

Conclusions:

• TIS is a critical mechanism of breast cancer drug resistance.
• The SASP plays a dual role, initially hindering but ultimately promoting tumor progression and recurrence.
• Targeting senescent cancer cells presents a promising therapeutic avenue to overcome resistance and prevent recurrence.