Having devoted a major portion of my 35-year medical career to reading the scientific literature, I have gotten to know some of the world’s leading oncobiologists (cancer scientists). Sometimes I come across scientists whose findings from animal studies look so promising and compelling, they cry out to be implemented in humans, especially when a stage-4 cancer patient is quickly running out of time. One such finding has to do with targeting senescence cancer cells.
Not all cancer cells can be forced into apoptosis (programmed cell death) when treated with chemotherapy. Instead of dying outright, many cancer cells simply stop proliferating, come to a standstill, and enter a senescent or dormant-like state. This is called senescence-associated growth arrest (SAGA), and while it sounds good, it is accompanied by something bad called senescence-associated secretory phenotype (SASP) in which the senescent cancer cells secrete copious amounts of pro-inflammatory molecules, protein-degrading compounds, and cancer-promoting growth factors. These harmful compounds not only promote the adverse effects of treatment, but also promote the proliferation of cancer stem cells which can repopulate the tumor with new cancer cells leading to treatment failure or eventual cancer recurrence after remission.
Many chemotherapy drugs act as “senogenic” agents, meaning, they induce senescence in cancer cells. However, when combined with “senolytic” drugs, meaning, repurposed drugs shown to eradicate senescent cells, scientists found this to be a novel and powerful “one-two punch” to quickly eradicate cancer cells. In other words, using chemotherapy to kill cancer cells and create a population of senescent cancer cells, then killing the senescent cells using senolytic drugs. One promising senolytic drug that is readily available is digoxin.
Comments from Dr. Thomas: Digoxin has a narrow therapeutic index. To reduce the incidence of digoxin toxicity, proper dosing and medical monitoring are important. Fortunately, the incidence of toxicity has been found to be substantially reduced by the use of intermittent low-dose digoxin.
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