Rapalogs in cancer prevention Anti-aging or anticancer?

被引：65

作者：

Blagosklonny, Mikhail V. ^{[1
]}

机构：

[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA

来源：

CANCER BIOLOGY & THERAPY | 2012年 / 13卷 / 14期

关键词：

aging; senescence; geroconversion; gerosuppression; rapamycin; diseases; mTOR; TRANSGENIC MOUSE MODEL; AGE-RELATED DISEASES; HEALTHY LIFE-SPAN; CALORIE RESTRICTION; CELL-CYCLE; SPONTANEOUS TUMORIGENESIS; THERAPEUTIC TARGET; MTOR INHIBITION; KAPOSIS-SARCOMA; PI3K PATHWAY;

D O I：

10.4161/cbt.22859

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1349 / 1354

页数：6

共 140 条

[1] Targeting mTOR for the treatment of AML. New agents and new directions. [J].

Altman, Jessica K. ;

Sassano, Antonella ;

Platanias, Leonidas C. .

ONCOTARGET, 2011, 2 (06) :510-517

[2] Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span [J].

Andersen, Stacy L. ;

Sebastiani, Paola ;

Dworkis, Daniel A. ;

Feldman, Lori ;

Perls, Thomas T. .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2012, 67 (04) :395-405

[3] Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice [J].

Anisimov, Vladimir N. ;

Zabezhinski, Mark A. ;

Popovich, Irina G. ;

Piskunova, Tatiana S. ;

Semenchenko, Anna V. ;

Tyndyk, Margarita L. ;

Yurova, Maria N. ;

Rosenfeld, Svetlana V. ;

Blagosklonny, Mikhail V. .

CELL CYCLE, 2011, 10 (24) :4230-4236

[4] Rapamycin Extends Maximal Lifespan in Cancer-Prone Mice [J].

Anisimov, Vladimir N. ;

Zabezhinski, Mark A. ;

Popovich, Irina G. ;

Piskunova, Tatiana S. ;

Semenchenko, Anna V. ;

Tyndyk, Margarita L. ;

Yurova, Maria N. ;

Antoch, Marina P. ;

Blagosklonny, Mikhail V. .

AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (05) :2092-2097

[5] Identification of Akt-selective cytotoxic compounds that enhance cytotoxic responses to rapamycin [J].

Barger, Jennifer F. ;

Gallo, Catherine A. ;

Torni, Kyle A. ;

Merk, Lisa ;

Seibel, William L. ;

Nelson, Sandra ;

Plas, David R. .

CANCER BIOLOGY & THERAPY, 2010, 10 (12) :1256-1261

[6] Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice [J].

Berrigan, D ;

Perkins, SN ;

Haines, DC ;

Hursting, SD .

CARCINOGENESIS, 2002, 23 (05) :817-822

[7] The two TORCs and Akt [J].

Bhaskar, Prashanth T. ;

Hay, Nissim .

DEVELOPMENTAL CELL, 2007, 12 (04) :487-502

[8] Pharmacologic synergy between dual phosphoinositide-3-kinase and mammalian target of rapamycin inhibition and 5-Fluorouracil in PIK3CA mutant gastric cancer cells [J].

Bhattacharya, Bhaskar ;

Akram, Mohamed ;

Balasubramanian, Indirakumar ;

Tam, Kimberley K. Y. ;

Koh, King X. ;

Yee, Mei Q. ;

Soong, Richie .

CANCER BIOLOGY & THERAPY, 2012, 13 (01) :34-42

[9] A longer and healthier life with TOR down-regulation: genetics and drugs [J].

Bjedov, Ivana ;

Partridge, Linda .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2011, 39 :460-465

[10] Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster [J].

Bjedov, Ivana ;

Toivonen, Janne M. ;

Kerr, Fiona ;

Slack, Cathy ;

Jacobson, Jake ;

Foley, Andrea ;

Partridge, Linda .

CELL METABOLISM, 2010, 11 (01) :35-46

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