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Senolytics and senescence-directed therapy

Chemotherapy leaves behind zombie cells that will not divide but poison their neighbours. Senolytics aim to clear them.

Therapy-induced senescent cells secrete inflammatory factors that promote relapse, drive fatigue, and accelerate ageing in survivors. Preclinically, a one-two punch of a senescence-inducing drug followed by a senolytic such as navitoclax improves outcomes. In humans, senolytic trials are concentrated in ageing, osteoporosis and neurodegeneration: a September 2026 registry search found no phase 2 senolytic study in cancer survivors. Navitoclax's thrombocytopenia limits dosing.

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Structured aerobic + resistance

How it works

Senescent cells depend on anti-apoptotic BCL-2 family proteins to survive; BH3 mimetics, or dasatinib plus quercetin, kill them selectively.

Strengths
  • Could reduce both relapse and long-term treatment toxicity
  • Intermittent dosing may suffice
  • Existing drugs available for repurposing
Limitations
  • Almost no oncology clinical data
  • Navitoclax causes thrombocytopenia
  • Senescence is protective as well as harmful, so timing matters

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