One-two punch: clear senescent cells after chemotherapy

This idea proposes a one-two punch: chemotherapy leaves senescent cells that inflame tissues and help tumours relapse, so a short senolytic course afterwards might cut relapse and late side effects at once. Therapy-induced senescence promotes relapse, cachexia and frailty in models, and senolytics (navitoclax, BCL-XL PROTACs, dasatinib plus quercetin) and uPAR CAR-T clear such cells preclinically (Cellular senescence pathway). The hypothesis is that senolytic consolidation reduces relapse and frailty in patients with a high senescence burden measured by p16, and platelet-sparing BCL-XL degraders remove the toxicity barrier. The test is a randomised phase 2 of such a degrader against placebo after adjuvant chemotherapy in Triple-negative breast cancer (TNBC) or Ovarian cancer.