Villegas VCA, Frontela NM, García FI

Idioma: Español
Referencias bibliográficas: 39
Paginas: 80-90
Archivo PDF: 133.80 Kb.

RESUMEN

La metformina es una biguanida ampliamente usada en el tratamiento de la diabetes mellitus tipo 2. Evidencias recientes proponen nuevos usos para esta vieja droga. El cáncer, que constituye un problema de salud mundial, se desarrolla con más frecuencia y peor pronóstico en los pacientes con diabetes tipo 2. Sin embargo, se ha comprobado que cuando estos son tratados con metformina presentan menor incidencia, complicaciones y mortalidad por cáncer. Por tal motivo, durante casi una década, se llevaron a cabo numerosas investigaciones epidemiológicas, básicas, preclínicas y ensayos clínicos, para fundamentar las evidencias del efecto protector y antitumoral de este medicamento. En tal sentido, se encontró que posee efectos antineoplásicos, por mecanismos sensibilizadores de la insulina, y otros, como que son pro-apoptóticos, que alteran el desarrollo de la célula madre cancerosa e interfieren con la carcinogénesis. Esto ha abierto una amplia gama de aplicaciones de la metformina en la terapéutica del cáncer, que abarcan desde los efectos preventivos, hasta las coadyuvantes de los tratamientos estándares.

REFERENCIAS (EN ESTE ARTÍCULO)

1. WHO. GLOBOCAN; 2012. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 [homepage en Internet]; actualizado 2012 [citado 3 de enero de 2016]. Disponible en: http://globocan.iarc.fr/Pages/summary_table_site_sel.aspx

2. Cuba. Minsap. Anuario estadístico de salud. 2012 [homepage en Internet]; La Habana, 2013 [citado 3 de enero de 2016]. Disponible en: www.sld.cu/sitios/dne

3. Inoue M, Tsugane S. Insulin resistance and cancer: epidemiological evidence. Endocr Relat Cancer. 2012;19(5):1-8.

4. Zhang PH, Chen ZW, Lv D, Xu YY, Gu WL, Zhang XH, et al. Increased risk of cancer in patients with type 2 diabetes mellitus: A retrospective cohort study in China. BMC Public Health. 2012;12:567-80.

5. Wang M, Hu RY, Wu HB, Pan J, Gong WW, Guo LH, et al. Cancer risk among patients with type 2 diabetes mellitus: a population-based prospective study in China. Sci Rep. 2015;5:11503.

6. Luo J, Beresford S, Chen C, Chlebowski R, Garcia L, Kuller L, et al. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer. 2014;111:1432-9.

7. Turati F, Polesel J, Di Maso M, Montella M, Libra M, Grimaldi M, et al. Diabetes mellitus and the risk of bladder cancer: an Italian case-control study. Br J Cancer. 2015;113:127-30.

8. Holden SE. Diabetes and Cancer. Endocr Dev. 2016;31:135-45.

9. Yang X, Heung M, Lee JC, Chan N. Drug–subphenotype interactions for cancer in type 2 diabetes mellitus. Nat Rev Endocr. 2015;11:372-9.

10. Xu HL, Fang H, Xu WH, Qin GY, Yan YJ, Yao BD, et al. Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai. BMC Cancer. 2015;15:852.

11. Hart T, Dider S, Han W, Xu H, Zhao Z, Xie L. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology. Sci Rep. 2016;6:1-13.

12. Landman GW, Kleefstra N, Van Hateren KJ, Groenier KH, Gans RO, Bilo HJ. La metformina se asoció a una menor mortalidad por cáncer en la diabetes tipo 2: ZODIAC-16. Diabetes Care. 2010;33:322-6.

13. Taubes G. Cancer Prevention with a Diabetes Pill? Science. 2012;335(6064):29.

14. Mao Y, Tao M, Jia X, Xu H, Chen K, Tang H, et al. Effect of Diabetes Mellitus on Survival in Patients with Pancreatic Cancer: A Systematic Review and Metaanalysis. Sci Rep. 2015;5:17102.

15. Shaw RJ, Cantley LC. Ancient Sensor for Ancient Drug. Science. 2012;336:813-4.

16. Martin Castillo B, Vazquez Martin A, Oliveras Ferraros C, Menendez JA. Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena. Cel Cycle. 2010;9(6):1057-64.

17. Bost F, Decoux Poullot AG, Tanti JF, Clavel S. Energy disruptors: rising stars in anticancer therapy? Oncogenesis. 2016;5:188.

18. Feng W, Jia YY, Zhang DY, Shi HR. Management of polycystic ovarian syndrome with Diane-35 or Diane-35 plus metformin. Gynecol Endocrinol. 2016;32(2):147-50.

19. Rajabi S, Mazloom Z, Zamani A, Tabatabaee HR. Effect of Low Glycemic Index Diet versus Metformin on Metabolic Syndrome. Int J Endocrinol Metab. 2015;13(4):e23091.

20. De Fronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-9.

21. Del Barco S, Vazquez Martin A, Cufí S, Oliveras Ferraros C, Bosch Barrera J, Joven J, et al. Metformin: Multi-faceted protection against cancer. Oncotarget. 2011;2(12):896-917.

22. Goto A, Noda M, Sawada N, Kato M, Hidaka A, Mizoue T, et al. High hemoglobin A1c levels within the non-diabetic range are associated with the risk of all cancers. Int J Cancer. 2016;138(7):1741-53.

23. Guo Q, Liu Z, Jiang L, Liu M, Ma J, Yang C, et al. Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase. Mol Med Rep. 2016;13(3):2590-6.

24. Huang D, He X, Zou J, Guo P, Jiang S, Lv N, et al. Negative regulation of Bmi-1 by AMPK and implication in cancer progression. Oncotarget. 2015;7(5):6188-200.

25. Han D, Li SJ, Zhu YT, Liu L, Li MX. LKB1/AMPK/mTOR signaling pathway in nonsmall- cell lung cancer. Asian Pac J Cancer Prev. 2013;14(7):4033-9.

26. Bo S, Benso A, Durazzo M, Ghigo E. Does use of metformin protect against cancer in Type 2 diabetes mellitus? J Endocrinol Invest. 2012;35(2):231-5.

27. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science. 2010;324(5930):1029-33.

28. Martinez Outschoorn U, Sotgia F, Lisanti MP. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin Oncol. 2014;41:195-216.

29. Marini C, Bianchi G, Buschiazzo A, Ravera S, Martella R, Bottoni G, et al. Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer. Sci Rep. 2016;6:19569.

30. Yanglei J, Zengyi M, Xiaofei L, Wenjing Z, Shan H, Xia X, et al. Metformin prevents DMH-induced colorectal cancer in diabetic rats by reversing the warburg effectbetic rats by reversing the Warburg effect. Cancer Med. 2015 Nov;4(11):1730-41.

31. Salani B, Del Rio A, Marini C, Sambuceti G, Cordera R, Maggi D. Metformin, cancer and glucose metabolism. Endocr Relat Cancer. 2014;21:461-71.

32. De Souza A, Khawaja K, Masud F, Wasif M. Metformin and pancreatic cancer: Is there a role? Cancer Chem Pharm. 2016;77(2):235-42.

33. Zhang R, Zhang P, Wang H, Hou D, Li W, Xiao G, et al. Inhibitory effects of metformin at low concentration on epithelial-mesenchymal transition of CD44+ CD117+ ovarian cancer stem cells. Stem Cell Res Ther. 2015;6:262.

34. Di Francesco AM, Toesca A, Cenciarelli C, Giordano A, Gasbarrini A, Puglisi MA. Metabolic Modification in Gastrointestinal Cancer Stem Cells: Characteristics and Therapeutic Approaches. J Cell Physiol. 2016;21:21-9.

35. Hattori Y, Hattori K, Hayashi T. Pleiotropic Benefits of Metformin: Macrophage Targeting Its Anti-inflammatory Mechanisms. Diabetes. 2015;64(6):1907-9.

36. Oliveras Ferraros C, Cufí S, Vazquez Martin A, Menendez OJ, Bosch Barrera J, Martin Castillo M, et al. Metformin rescues cell surface major histocompatibility complex class I (MHC-I) deficiency caused by oncogenic transformation. Landes Biosci. 2012;11(5):865-70.

37. Prlic M, Bevan MJ. Immunology: A metabolic switch to memory. Nature. 2009;460(7251):41-2.

38. Zarrouk M, Finlay DK, Foretz M, Viollet B, Cantrell DA. Adenosine-monophosphate- activated protein kinase-independent effects of metformin in T cells. PLoS One. 2014;9(9):e106710.

39. Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci USA. 2015;112(6):1809-14.