Rapalogs in Cancer Prevention: Anti-aging or Anticancer?

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2012 Nov 16

PMID 23151465

Citations 57

Authors

Mikhail V Blagosklonny

Affiliations

Soon will be listed here.

Abstract

Common cancer is an age-related disease. Slow aging is associated with reduced and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging intervention, prevents cancer by slowing down the aging process. Evidence is emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin). Rapamycin and other rapalogs suppress cellular senescence, slow down aging and postpone age-related diseases including cancer. At the same time, rapalogs are approved for certain cancer treatments. Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario.

Citing Articles

The "Road" to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review.

Hablase R, Kyrou I, Randeva H, Karteris E, Chatterjee J Cancers (Basel). 2024; 16(11).

PMID: 38893278 PMC: 11172073. DOI: 10.3390/cancers16112160.

Unconventional mechanism of action and resistance to rapalogs in renal cancer.

Yang J, Butti R, Cohn S, Toffessi-Tcheuyap V, Mal A, Nguyen M Proc Natl Acad Sci U S A. 2024; 121(25):e2310793121.

PMID: 38861592 PMC: 11194491. DOI: 10.1073/pnas.2310793121.

An Observatory for the Oncogene: A Guide for Targeted Therapies.

Altintas D, Comoglio P Cancers (Basel). 2023; 15(18).

PMID: 37760640 PMC: 10526818. DOI: 10.3390/cancers15184672.

Metabolism and senescence in the immune microenvironment of osteosarcoma: focus on new therapeutic strategies.

Ying H, Li Z, Li M, Liu W Front Endocrinol (Lausanne). 2023; 14:1217669.

PMID: 37497349 PMC: 10366376. DOI: 10.3389/fendo.2023.1217669.

Anti-aging Strategies and Topical Delivery of Biopolymer-based Nanocarriers for Skin Cancer Treatment.

Ramaraj J, Narayan S Curr Aging Sci. 2023; 17(1):31-48.

PMID: 36941817 DOI: 10.2174/1874609816666230320122018.

References

Andersen S, Sebastiani P, Dworkis D, Feldman L, Perls T . Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci. 2012; 67(4):395-405. PMC: 3309876. DOI: 10.1093/gerona/glr223. View

Mita M, Mita A, Rowinsky E . The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther. 2003; 2(4 Suppl 1):S169-77. View

Minor R, Allard J, Younts C, Ward T, de Cabo R . Dietary interventions to extend life span and health span based on calorie restriction. J Gerontol A Biol Sci Med Sci. 2010; 65(7):695-703. PMC: 2884086. DOI: 10.1093/gerona/glq042. View

Moskalev A, Shaposhnikov M . Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster. Rejuvenation Res. 2009; 13(2-3):246-7. DOI: 10.1089/rej.2009.0903. View

Blagosklonny M . Carcinogenesis, cancer therapy and chemoprevention. Cell Death Differ. 2005; 12(6):592-602. DOI: 10.1038/sj.cdd.4401610. View

Garrett J, Chakrabarty A, Arteaga C . Will PI3K pathway inhibitors be effective as single agents in patients with cancer?. Oncotarget. 2012; 2(12):1314-21. PMC: 3282088. DOI: 10.18632/oncotarget.409. View

Kaeberlein M, Powers 3rd R, Steffen K, Westman E, Hu D, Dang N . Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005; 310(5751):1193-6. DOI: 10.1126/science.1115535. View

Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S . Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004; 14(10):885-90. PMC: 2754830. DOI: 10.1016/j.cub.2004.03.059. View

Blagosklonny M . Antiangiogenic therapy and tumor progression. Cancer Cell. 2004; 5(1):13-7. DOI: 10.1016/s1535-6108(03)00336-2. View

10.

Ikeno Y, Bronson R, Hubbard G, Lee S, Bartke A . Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003; 58(4):291-6. DOI: 10.1093/gerona/58.4.b291. View

11.

Markman B, Dienstmann R, Tabernero J . Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs. Oncotarget. 2011; 1(7):530-543. PMC: 3248125. DOI: 10.18632/oncotarget.188. View

12.

Weber G, Parat M, Binder Z, Gallia G, Riggins G . Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells. Oncotarget. 2011; 2(11):833-49. PMC: 3260001. DOI: 10.18632/oncotarget.346. View

13.

Blagosklonny M . Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives. Aging (Albany NY). 2010; 2(5):265-73. PMC: 2898017. DOI: 10.18632/aging.100149. View

14.

Galluzzi L, Kepp O, Kroemer G . TP53 and MTOR crosstalk to regulate cellular senescence. Aging (Albany NY). 2010; 2(9):535-7. PMC: 2984599. DOI: 10.18632/aging.100202. View

15.

Majumder S, Caccamo A, Medina D, Benavides A, Javors M, Kraig E . Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell. 2012; 11(2):326-35. PMC: 3306461. DOI: 10.1111/j.1474-9726.2011.00791.x. View

16.

Mathew T, Kreis H, Friend P . Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant. 2004; 18(4):446-9. DOI: 10.1111/j.1399-0012.2004.00188.x. View

17.

Blagosklonny M . Molecular damage in cancer: an argument for mTOR-driven aging. Aging (Albany NY). 2012; 3(12):1130-41. PMC: 3273893. DOI: 10.18632/aging.100422. View

18.

Henry C, Marusyk A, DeGregori J . Aging-associated changes in hematopoiesis and leukemogenesis: what's the connection?. Aging (Albany NY). 2011; 3(6):643-56. PMC: 3164372. DOI: 10.18632/aging.100351. View

19.

Ye J, Keller J . Regulation of energy metabolism by inflammation: a feedback response in obesity and calorie restriction. Aging (Albany NY). 2010; 2(6):361-8. PMC: 2919256. DOI: 10.18632/aging.100155. View

20.

Hart J, Vogt P . Phosphorylation of AKT: a mutational analysis. Oncotarget. 2011; 2(6):467-76. PMC: 3139455. DOI: 10.18632/oncotarget.293. View