Rapalogs in cancer prevention

Targeting multiple tyrosine kinase receptors with Dovitinib blocks invasion and the interaction between tumor cells and cancer-associated fibroblasts in breast cancer

“…We provide a new evidence for the increasingly accepted view that both cancer and aging share the activation of a common signaling pathway, and targeting this pathway directly or indirectly will retard breast cancer progression. 33,36 Our data suggest a new mechanism by which Dovitinib antagonizes the breast cancer metastasis.…”

“…In turn, aging cells due to their hyperfunctions cause diseases of aging including cancer. 33 In this context, anti-tumor effect of PI3K/Akt/mTOR pathway inhibitors was not only achieved by significantly inhibiting the tumor cell proliferation and division, but also by targeting tumor stroma, for example decreasing the stromal content, and reducing the levels of both vimentin and phospho-S6 (2 known markers for cell aging) in aging CAFs model. 31 Recent publications demonstrated with in vitro experiments, mouse models and clinical trials that Dovitinib showed antitumor activity in FGFR-amplified breast cancer.…”

Gerometabolites: The pseudohypoxic aging side of cancer oncometabolites

“…58,59 The prolonged stimulation of mTOR in normal cells can lead to stem cell depletion and reduced organismal health and life span, and mTOR activation is a common feature in most human malignancies. Although the ultimate molecular mechanism(s) underlying the aimless continuation of developmental growth driven by nutrient-sensing, growth-promoting signaling pathways such as the mTOR gerogene are not completely understood, it should be noted that the hyperfunctions (aging), loss of homeostasis, and age-related disease (cancer) triggered by the continuous postdevelopmental activity of such gerogenic pathways [60][61][62][63][64][65][66][67][68][69][70][71] can be easily linked to the pseudo-hypoxic scenario triggered by the accumulation of oncometabolites and the decline of gerometabolites.…”

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

“…1 Rapamycin extends life span in mice. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Furthermore, rapamycin delays the onset of cancer in mice.…”

“…[3][4][5][6][7][9][10][11][12][13]15,18 Rapamycin and everolimus (a rapamycin analog) decrease the risk of cancer in humans, who receive these rapalogs to prevent transplant rejection. 1,[21][22][23][24] Therefore, rapalogs such as rapamycin are considered for both prevention of cancer and extension of healthy life span in humans. [25][26][27][28][29][30][31] There is a concern that potential side effects may limit rapamycin use as anti-aging drug.…”