Rapamycin delays cancer by slowing down ageing and targeting pre-cancerous cells: Study

USA: In a new research perspective published in the journal Oncotarget, Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center discussed rapamycin and other rapalogs and their potential to delay cancer by targeting pre-cancerous cells and slowing down organismal ageing.

The mTOR (Target of Rapamycin) pathway is involved in cancer and ageing. Furthermore, common cancers are age-related diseases, and their incidence increases exponentially.

“Rapamycin (sirolimus) and other rapalogs (everolimus) are anti-cancer and anti-ageing drugs, which delay cancer by directly targeting pre-cancerous cells and, indirectly, by slowing down organism ageing.”

Cancer is an age-related disease; figuratively, rapamycin may delay cancer by slowing down time (and ageing). In several dozen murine models, rapamycin robustly and reproducibly prevents cancer. Rapamycin slows cell proliferation and tumour progression, thus delaying the onset of cancer in carcinogen-treated, genetically cancer-prone and normal mice. Data on the use of rapamycin and everolimus in organ-transplant patients are consistent with their cancer-preventive effects. Treatment with rapamycin was proposed to prevent lung cancer in smokers and former smokers. Clinical trials in high-risk populations are warranted.

“Currently, an increasing number of healthy people use rapamycin off-label to slow down ageing. Perhaps in ten or twenty years, data will accumulate for retrospective analysis of cancer prevention with rapamycin in humans.”

Blagosklonny wrote, "Rapamycin robustly and reproducibly delays cancer and sometimes prevents cancer over a lifetime in several dozen murine models. He noted that it was repeatably proposed that clinical trials in high-risk populations are warranted. He says that a decade-long treatment with rapamycin may be employed to prevent lung cancer in smokers and former smokers.

"Accidental data on using rapamycin (Sirolimus) and everolimus in organ-transplant patients is consistent with their cancer-preventive effects," he added/ "However, in these patients, their use in combination with other immunosuppressants makes interpretations difficult."

"The treatment experience of cancer patients with mTOR inhibitors also agrees with their cancer-preventive effects," says Dr Blagosklonny. "Although rapalogs do not cure cancer and cause remission infrequently, they can slow down progression even in advanced tumours, and this activity is sufficient for cancer prevention."

He further added that long-term treatment with rapamycin slows down ageing, a major risk factor for cancer. Notably, delaying cancer is a form of cancer prevention.

"Consider a scenario: rapamycin delays cancer for two years, during which this person dies from myocardial infarction. In this case, postponing cancer is cancer prevention," he concludes. 

Reference:

Mikhail V. Blagosklonny, Cancer prevention with rapamycin, Oncotarget (2023). DOI: 10.18632/oncotarget.28410.