OnCo
ideasIdea

One-two punch: clear senescent cells after chemotherapy

Chemotherapy leaves behind senescent cells that inflame tissues and help tumours relapse. A short course of senolytic drugs afterwards might reduce relapse and long-term side effects at once.

Therapy-induced senescence and SASP promote relapse, cachexia, and frailty in models; senolytics (navitoclax, BCL-XL PROTACs, dasatinib+quercetin) clear them in mice; uPAR CAR-T clears senescent cells preclinically.

Hypothesis
Senolytic consolidation after chemotherapy reduces relapse and treatment-related frailty in patients with high post-treatment senescence burden (p16 expression in blood cells or tumour).
Rationale
Lowe, Demaria, and Kirkland preclinical data; p16INK4a in T cells is a validated senescence biomarker; platelet-sparing BCL-XL degraders remove the main toxicity barrier.
What would test it
Randomised phase 2 of a platelet-sparing BCL-XL degrader vs placebo after adjuvant chemotherapy in TNBC or ovarian cancer, endpoints DFS and geriatric-assessment frailty scores.
Maturity
preclinical evidence

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