Ramos-Peñafiel CO, Santoyo-Sánchez A, Olarte-Carrillo I, Queipo-García GE, Garfias-Becerra Y, Martínez-Tovar A

Idioma: Español
Referencias bibliográficas: 59
Paginas: 168-178
Archivo PDF: 901.50 Kb.

RESUMEN

Al día de hoy se sabe que en la génesis y mantenimiento efectivo de una célula tumoral participan el mantenimiento de señales de proliferación celular, la evasión de los mecanismos supresores, resistencia a la apoptosis, replicación ilimitada, inducción de la angiogénesis, invasión y metástasis. Recientemente se han postulado también las alteraciones al equilibrio energético celular y la expresión de genes de resistencia a múltiples fármacos. La metformina, un medicamento prescrito durante más de 50 años, es en la actualidad el patrón de referencia en el tratamiento de pacientes diabéticos no insulinodependientes debido a que tiene mecanismos de acción capaces de regular los mecanismos de obtención de energía. A partir de la administración tan difundida de este fármaco en todo el mundo, surgieron diversas cohortes que apuntaban a que metformina era un factor protector contra el cáncer. Esta teoría se ha trasladado de manera exitosa a experimentos in vitro e in vivo, confirmándose las propiedades antitumorales, al parecer, mediadas por la inhibición de la vía LBK1/AMPK/mTOR y del IGF-1R. Por esta razón, en apenas menos de una década es posible encontrar ensayos clínicos de la adición de metformina a los esquemas de quimioterapia contra casi todos los tipos de cáncer. Sin duda alguna, se seguirán generando y consolidando los conocimientos de los efectos de metformina descritos e incluso de otros más inesperados, como los efectos sinérgicos que parece tener con los antibióticos en el tratamiento de la tuberculosis multirresistente.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Torre LA, Bray F, Siegel RL, Ferlay J, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.

2. Edwards BK, Noone AM, Mariotto AB, Simard EP, et al. Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 2014;120:1290-1314.

3. Bazargan M, Bazargan SH, Farooq M, Baker RS. Correlates of cervical cancer screening among underserved Hispanic and African-American women. Prev Med (Baltim) 2004;39:465-473.

4. Meneses-García A, Ruiz-Godoy LM, Beltrán-Ortega A, Sánchez-Cervantes F y col. Principales neoplasias malignas en México y su distribución geográfica (1993-2002). Rev Invest Clin 2012;64:322-329.

5. Pérez-Saldivar ML, Fajardo-Gutiérrez A, Bernáldez-Ríos R, Martínez-Avalos A, et al. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology. BMC Cancer 2011;11:355.

6. González-Salas WM, Olarte-Carrillo I, Gutiérrez-Romero M, Montaño-Figueroa EH, et al. Frecuencia de leucemias agudas en un hospital de referencia. Rev Med Inst Mex Seguro Soc 2012;50:167-171.

7. Estadística a propósito del día mundial contra el cáncer. Instituto Nacional de Estadística y Geografía [Internet]. México, D.F., México; 2015 [Consultado 4 abril 2015]. Disponible en: http://www.inegi.org.mx/inegi/default.aspx?s=inegi&c=269

8. Pan J, Chen C, Jin Y, Fuentes-Mattei E, et al. Differential impact of structurally different anti-diabetic drugs on proliferation and chemosensitivity of acute lymphoblastic leukemia cells. Cell Cycle 2012;11:2314-2326.

9. Ramos-Peñafiel CO, Martínez-Murillo C, Santoyo-Sánchez A, Jiménez-Ponce F, et al. [Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy treatment]. Rev Med Inst Mex Seguro Soc 2014;52:270-275.

10. Horne SD, Pollick SA, Heng HHQ. Evolutionary mechanism unifies the hallmarks of cancer. Int J Cancer 2015;136:2012-2021.

11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-674.

12. Sonnenschein C, Soto AM. The aging of the 2000 and 2011 Hallmarks of Cancer reviews: a critique. J Biosci 2013;38:651-663.

13. Marín de Mas I, Aguilar E, Jayaraman A, Polat IH, et al. Cancer cell metabolism as new targets for novel designed therapies. Future Med Chem 2014;6:1791-1810.

14. Masoudi-Nejad A, Asgari Y. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment. Semin Cancer Biol 2015;30:21-29.

15. Lopes-Ribeiro A, Keith-Okamoto O. Combined effects of pericytes in the tumor microenvironment. Stem Cells Int 2015;2015:8.

16. Romano A, Conticello C, Cavalli M, Vetro C, et al. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int 2014;2014:198539.

17. Kharaishvili G, Simkova D, Bouchalova K, Gachechiladze M, et al. The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance. Cancer Cell Int 2014;14:41.

18. Kawaguchi M, Kataoka H. Mechanisms of hepatocyte growth factor activation in cancer tissues. Cancers (Basel) 2014;6:1890-1904.

19. Liu H, Lv L, Yang K. Chemotherapy targeting cancer stem cells. Am J Cancer Res 2015;5:880-893.

20. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005;65:385-411.

21. Chan K, Truong D, Shangari N, O’Brien PJ. Drug-induced mitochondrial toxicity. Expert Opin Drug Metab Toxicol 2005;1:655-669.

22. Emami Riedmaier A, Fisel P, Nies AT, Schaeffeler E, Schwab M. Metformin and cancer: from the old medicine cabinet to pharmacological pitfalls and prospects. Trends Pharmacol Sci 2013;34:126-135.

23. Bowker SL, Yasui Y, Veugelers P, Johnson JA. Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Diabetologia 2010;53:1631-1637.

24. Zhang Z-J, Zheng Z-J, Kan H, Song Y, et al. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care 2011;34:2323-2328.

25. Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat 2012;135:639-646.

26. Baur DM, Klotsche J, Hamnvik O-PR, Sievers C, et al. Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort. Metabolism 2011;60:1363-1371.

27. Liu B, Fan Z, Edgerton SM, Deng X-S, et al. Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle 2009;8:2031-2040.

28. Koh M, Lee J-C, Min C, Moon A. A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells. Bioorg Med Chem 2013;21:2305-2313.

29. Kim HJ, Kwon H, Lee JW, Kim HJ, et al. Metformin increases survival in hormone receptor-positive, Her2-positive breast cancer patients with diabetes. Breast Cancer Res 2015;17:64.

30. Dowling RJO, Niraula S, Stambolic V, Goodwin PJ. Metformin in cancer: translational challenges. J Mol Endocrinol 2012;48:R31-R43.

31. Serrano M. Metformin and reprogramming into iPSCs. Cell Cycle 2012;11:1058-1059.

32. Feng Y-H, Wu C-L, Shiau A-L, Lee J-C, et al. MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. Int J Mol Med 2012;29:920-926.

33. Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells. Curr Mol Med 2010;10:674-691.

34. Pernicova I, Korbonits M. Metformin–mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol 2014;10:143-156.

35. Memmott RM, Mercado JR, Maier CR, Kawabata S, et al. Metformin prevents tobacco carcinogen–induced lung tumorigenesis. Cancer Prev Res (Phila) 2010;3:1066-1076.

36. Xie Y, Wang Y-L, Yu L, Hu Q, et al. Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol 2011;126:113-120.

37. Micic D, Cvijovic G, Trajkovic V, Duntas LH, Polovina S. Metformin: its emerging role in oncology. Hormones (Athens) 2011;10:5-15.

38. Rozengurt E, Sinnett-Smith J, Kisfalvi K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G proteincoupled receptor signaling systems: A novel target for the antidiabetic drug metformin in pancreatic cancer. Clin Cancer Res 2010;16:2505-2511.

39. Dirat B, Ader I, Golzio M, Massa F, Mettouchi A, et al. Inhibition of the GTPase Rac1 mediates the antimigratory effects of metformin in prostate cancer cells. Mol Cancer Ther 2015;14:586-596.

40. Nakamura M, Ogo A, Yamura M, Yamaguchi Y, Nakashima H. Metformin suppresses sonic hedgehog expression in pancreatic cancer cells. Anticancer Res 2014;34:1765-1769.

41. Fan C, Wang Y, Liu Z, Sun Y, et al. Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer. Int J Mol Med 2015 May 21 [Epub ahead of print].

42. Lin C-C, Yeh H-H, Huang W-L, Yan J-J, et al. Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. Am J Respir Cell Mol Biol 2013;49:241-250.

43. Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003;22:8581-8589.

44. Yang J, Liu F-X, Yan X-C. [Research advances on inhibitor of apoptosis, survivin]. Ai Zheng 2003;22:771-774.

45. Yamamoto T, Tanigawa N. The role of survivin as a new target of diagnosis and treatment in human cancer. Med Electron Microsc 2001;34:207-212.

46. Lesan V, Ghaffari SH, Salaramoli J, Heidari M, et al. Evaluation of antagonistic effects of metformin with cisplatin in gastric cancer cells. Int J Hematol Stem cell Res 2014;8:12-19.

47. Han G, Gong H, Wang Y, Guo S, Liu K. AMPK/mTOR-mediated inhibition of survivin partly contributes to metformininduced apoptosis in human gastric cancer cell. Cancer Biol Ther 2015;16:77-87.

48. Vallianou NG, Evangelopoulos A, Kazazis C. Metformin and cancer. Rev Diabet Stud 2013;10:228-235.

49. Rosilio C, Ben-Sahra I, Bost F, Peyron J-F. Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia. Cancer Lett 2014;346:188-196.

50. Vakana E, Platanias LC. AMPK in BCR-ABL expressing leukemias. Regulatory effects and therapeutic implications. Oncotarget 2011;2:1322-1338.

51. Vakana E, Altman JK, Glaser H, Donato NJ, Platanias LC. Antileukemic effects of AMPK activators on BCR-ABLexpressing cells. Blood 2011;118:6399-6402.

52. Leclerc GM, Leclerc GJ, Kuznetsov JN, DeSalvo J, Barredo JC. Metformin induces apoptosis through AMPK-dependent inhibition of UPR signaling in ALL lymphoblasts. PLoS One 2013;8:e74420.

53. Ramos-Peñafiel CO, Olarte-Carrillo I, Martínez-Tovar A, Castellanos-Sinco H, et al. Effect of metformin to a pretreatment with steroids in adult patients with acute lymphoblastic leukemia and in the viability of the MOLT-4 cell line. Med UIS 2014;27:221-229.

54. Singhal A, Jie L, Kumar P, Hong GS, et al. Metformin as adjunct antituberculosis therapy. Sci Transl Med 2014;6:263ra159.

55. Vashisht R, Brahmachari SK. Metformin as a potential combination therapy with existing front-line antibiotics for tuberculosis. J Transl Med 2015;13:83.

56. Tran L, Zielinski A, Roach AH, Jende JA, et al. The Pharmacologic treatment of type 2 diabetes: Oral medications. Ann Pharmacother 2015;49:540-556.

57. Poomalar GK. Changing trends in management of gestational diabetes mellitus. World J Diabetes 2015;6:284-295.

58. Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes 2015;6:296-303.

59. Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol 2014;10:624-636.