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Senolytics are drugs meant to kill the worn-out cells that chemotherapy leaves behind. The idea is good and the animal work is striking. The human evidence is four small trials in other diseases, none in cancer survivors, and the one properly randomised trial missed its main target. Nobody should be buying these.
The best studied combination is dasatinib, a leukaemia drug, with quercetin, a plant flavonol, given intermittently rather than continuously. The first human study was open-label, in 14 people with idiopathic pulmonary fibrosis: walking distance, gait speed and chair-stand time improved significantly, there was no control group, and pulmonary function and the frailty index did not change. A second open-label study in nine people with diabetic kidney disease showed that three days of the combination reduced p16INK4a and p21CIP1 positive cells in fat and skin eleven days later, the first direct demonstration that a senolytic clears senescent cells in a person.
The only randomised trial of any size is in postmenopausal women, not survivors: 60 participants given intermittent dasatinib plus quercetin for 20 weeks. The primary endpoint, change in the bone resorption marker CTx, did not differ between groups (median -4.1 per cent against -7.7 per cent, P = 0.611). Bone formation (P1NP) rose by 16 per cent against control at two and four weeks but not at 20. In an exploratory subgroup with the highest T-cell p16 levels, CTx fell and radius bone density rose. No serious adverse events occurred. The authors call the subgroup a hypothesis for further study, and that is what it is.
Fisetin, another flavonol, is in trials but has no completed randomised result in cancer survivors. Navitoclax is a genuine senolytic in the laboratory but inhibits BCL-xL, which is what platelets depend on, so dose-limiting thrombocytopenia has constrained it in oncology since its first trials; that toxicity is the reason the field moved to BCL-xL-degrading PROTACs and to dasatinib-based regimens. Dasatinib is a prescription cancer drug with its own toxicity, including pleural effusion and bleeding, and it interacts with CYP3A4 inhibitors. Quercetin at trial doses is far above any dietary amount. OnCo holds this as a research idea, not an option; the idea record is linked below.
Senescent cells survive by upregulating anti-apoptotic networks (BCL-2 family, PI3K/AKT, p53/p21/serpins). Senolytics transiently disable those networks so that senescent cells, which sit in a pro-apoptotic internal environment, die while normal cells do not. Intermittent dosing follows from the mechanism: the cells do not come back immediately, so continuous exposure is not needed.
Query for this technology: (TITLE:"senolytic" OR ABSTRACT:"senolytic" OR TITLE:"senolytics" OR ABSTRACT:"senolytics" OR TITLE:"dasatinib plus quercetin" OR ABSTRACT:"dasatinib plus quercetin" OR TITLE:"fisetin senolytic" OR ABSTRACT:"fisetin senolytic"). Results are unfiltered search hits about Senolytics after cancer treatment, not a curated reading list.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Senescent cells and p16 after chemotherapy, Cellular senescence, What actually works after treatment, Late effects and survivorship toxicity and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.