Epigenetic cancer drugs and their role in anticancer therapy

Česká verzia

Authors: P. Klener
Authors place of work: I. interní klinika 1. lékařské fakulty UK a VFN v Praze, přednosta prof. MU Dr. Marek Trněný, CSc., a Ústav hematologie a krevní transfuze Praha, ředitel prof. MU Dr. Marek Trněný, CSc.
Published in the journal: Vnitř Lék 2013; 59(6): 463-465
Category: 80th birthday prof. MUDr. Karla Horkého, DrSc., FACP (Hon.)

Summary

Epigenetic modification have been causally linked to cancer development and progression, and are potentially reversible by treatments with epigenetic cancer drugs. The aim of this review is to give an overview of the basic current knowledge on molecular mechanisms of epigenetic cancer drugs and their possible clinical use. Many of them are in inclinical trials. However only two demethylating agents ie. inhibitors of DNA methyltransferase (5- azacytidin and decitabin) are approved in the treatment of myelodysplastic syndrome and a few inhibitors of histonacetylase (vorinostat, romidepsin and panobinostat) are approved in the treatment of hematological malignancies, particularly in refractory or relapsed cutaneous T‑ cell lymhoma.

Key words:
epigenetic cancer drugs – inhibitors of DNA methyltransferase – inhibitors of histondeacetylase

Zdroje

1. Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358: 1148– 1159.

2. Grønbaek K, Hother C, Jones PA. Epigenetic changes in cancer. APMIS 2007; 115: 1039– 1059.

3. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012; 150: 12– 27.

4. Gilbert J, Gore SD, Herman JG et al. The clinical application of targeting cancer through histone acetylation and hypomethylation. Clin Cancer Res 2004; 15: 4589– 4596.

5. van Vierken LE, Hurt EM, Hollingswort RE. The role of epigenetic regulation in stem cell and cancer. J Mol Med (Berl) 2012; 90: 791– 801.

6. Brueckner B, Kuck D, Lyko F. DNA methyltransferase inhibitors for cancer therapy. Cancer J 2007; 13: 17– 22.

7. Mani S, Herceg Z. DNA demethylating agents and epigenetic therapy of cancer. Adv Genet 2010; 70: 327– 340.

8. Billam M, Sobolewski D, Davidson N. Effect of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res Treat 2010; 120: 581– 592.

9. Lee MJ, Kim SY, Kummar S et al. Histone deacetylase inhibitors in cancer therapy. Cur Opin Oncol 2008; 20: 639– 649.

10. Martinez‑ Iglesias O, Ruiz‑ Liorente L, Sánchez‑ Martinez R et al. Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer. Clin Transl Oncol 2008; 10: 395– 398.

11. Min‑Jung L, Yeong Sang K, Ku Shivani K et al. Histone deacetylase inhibitors in cancer therapy. Curr Opin Oncol 2008; 20: 639– 649.

12. Garcia‑ Manero G. Demethylating agents in myeloid malignancies. Curr Opin Oncol 2008; 20: 705– 710.

13. Garcia‑ Manero G, Fenaux P. Hypomethylating agents and other novel strategies in myelodysplastic syndromes. J Clin Oncol 2011; 29: 516– 523.

14. Quintás‑ Cardama A, Ravandi F, Liu‑ Dumlao Tet al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood 2012; 120: 4840– 4845.

15. Khan O, LaThangue NB. Drug insight: histone deacetylase inhibitor‑based therapies for cutaneous T‑ cell lymphomas. Nat Clin Pract Oncol 2008; 5: 714– 726.

16. Szyf M. Epigenetis, DNA methylation, and chromatin modyfying drugs. Ann Rev Pharmacol Toxicol 2009; 49: 243– 263.

17. Younes A, Oki Y, Bociek RG et al. Mocetinostat for relapsed classical Hodgkin’s lymphoma: an open‑ label, single‑arm, phase 2 trial. Lancet Oncol 2011; 13: 1222– 1228.

18. Hřebáčková J, Hraběta J, Eckschlager T. Valproic acid in the complex therapy of malignant tumors. Curr Drug Targets 2010; 11: 361– 379.