Fisetin for Stage IV Cancer
Also known as: 3,3',4',7-Tetrahydroxyflavone
Fisetin's senolytic and pro-apoptotic effects target both cancer cells and senescent stromal cells in the tumor microenvironment.
Mechanism of Action
Fisetin inhibits PI3K/Akt survival signaling, induces apoptosis through caspase-3/9 activation, and clears senescent cells that secrete pro-tumorigenic SASP factors. It also inhibits topoisomerase II and CDK2/4, arresting cancer cell division.
General mechanism: Bioactive flavonoid. Senolytic (PI3K/Akt/mTOR), Nrf2 activator, GSK3β inhibitor, anti-inflammatory, pro-apoptotic in cancer cells.
Current Evidence
Preclinical evidence across colon, prostate, and lung cancer models. Phase II AFFIRM trial for aging endpoints provides dosing data. Cancer-specific trials are in early stages.
Clinical Status: Preclinical for cancer. Senolytic Phase II (AFFIRM) ongoing.
Safety Profile
Very safe. Low oral bioavailability. Liposomal formulations being developed. No significant side effects.
Key Research Questions
- Can fisetin senolytics clear therapy-resistant senescent cancer cells?
- Does fisetin enhance chemotherapy by removing SASP-producing stromal cells?