Hyperprogression under immunotherapy and mTOR (hypothesis)

Hyperprogression under immunotherapy and mTOR (hypothesis) Mikhail V. Blagosklonny Abstract: Immunotherapy involving Immune Checkpoint Inhibitors can cause rapid tumor growth, particularly in patients with MDM2 amplification. MDM2 and mTOR inhibitors may mitigate this and improve therapy outcomes. Importantly, MDM2 inhibitors block mTOR in cancer cells. As MDM2 inhibitors aren’t approved for human use, mTOR inhibitors … Continue Reading

Cancer prevention with rapamycin

      Cancer prevention with rapamycin   Mikhail V. Blagosklonny   Introduction The mTOR (Target of Rapamycin) pathway is involved in both cancer and aging. Furthermore, common cancers are age-related diseases, and their incidence increases exponentially with age. In theory, rapamycin (sirolimus) and other rapalogs (temsirolimus, everolimus) may delay cancer by targeting directly pre-cancerous … Continue Reading

How rapamycin prevents muscle loss and sarcopenia (first draft)

The effect of rapamycin, an anti-aging drug, on the muscle, was puzzling for a decade. It seemed paradoxical that rapamycin, an inhibitor of mTOR component 1 (mTORC1), prevents muscle loss and sarcopenia. Yet, this is well established [1-5]. How is that possibly possible?  The nutrient-sensing mTOR pathway increases protein synthesis and cellular mass growth. Furthermore, … Continue Reading

Rapamycin: time is now … unless it’s too late

In 2006, I published an article that aging is not caused by free radicals nor by any kind of molecule damage but instead is a quasi-program driven in part by mTOR (Target of Rapamycin). By sheer luck, mTOR inhibitors – Sirolimus (rapamycin) and Everolimus – were clinically available. As I summarized in 2006: “…all diseases of aging … Continue Reading