Will next-generation agents deliver on the promise of epigenetic hypomethylation therapy?
2015; Future Medicine; Volume: 7; Issue: 7 Linguagem: Inglês
10.2217/epi.15.66
ISSN1750-1911
AutoresJames N. Lowder, Pietro Taverna, Jean‐Pierre J. Issa,
Tópico(s)Histone Deacetylase Inhibitors Research
ResumoEpigenomicsVol. 7, No. 7 CommentaryWill next-generation agents deliver on the promise of epigenetic hypomethylation therapy?James N Lowder, Pietro Taverna & Jean-Pierre J IssaJames N Lowder*Author for correspondence: E-mail Address: james.lowder@astx.com Astex Pharmaceuticals, 4420 Rosewood Drive, Suite 200, Pleasanton, CA 92488, USA, Pietro Taverna Astex Pharmaceuticals, 4420 Rosewood Drive, Suite 200, Pleasanton, CA 92488, USA & Jean-Pierre J Issa Fels Institute, Temple University School of Medicine & Cancer Epigenetics Program, Fox Chase Cancer Center, Temple Health, 3307 North Broad Street, Room 154, Philadelphia, PA 19140, USAPublished Online:6 Nov 2015https://doi.org/10.2217/epi.15.66AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: azacitidinedecitabineguadecitabinehypomethylating agentsReferences1 Issa JP. Aging and epigenetic drift: a vicious cycle. J. Clin. Invest. 124(1), 24–29 (2014).Crossref, Medline, CAS, Google Scholar2 Lynch M. Rate, molecular spectrum, and consequences of human mutation. Proc. Natl Acad. Sci. USA 107(3), 961–968 (2010).Crossref, Medline, CAS, Google Scholar3 Momparler R, Goodman J. In vitro cytotoxic and biochemical effects of 5-aza-2′-deoxycytidine. Cancer Res. 37(6), 1636–1639 (1977).Medline, CAS, Google Scholar4 Oki Y, Issa JP. Epigenetic mechanisms in AML – a target for therapy. Cancer Treat. Res. 145, 19–40 (2010).Crossref, Medline, CAS, Google Scholar5 Karahoca M, Momparler RL. Pharmacokinetic and pharmacodynamic analysis of 5-aza-2′-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy. Clin. Epigenetics 5(3), 1–16 (2013).Medline, Google Scholar6 Negrotto S, Ng KP, Jankowska AM et al. CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors. Leukemia 26(2), 244–254 (2012).Crossref, Medline, CAS, Google Scholar7 Issa JP, Garcia-Manero G, Giles FJ et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103(5), 1635–1640 (2004).Crossref, Medline, CAS, Google Scholar8 Saunthararajah Y. Key clinical observations after 5-azacytidine and decitabine treatment of myelodysplastic syndromes suggest practical solutions for better outcomes. Hematology Am. Soc. Hematol. Educ. Program 2013, 511–521 (2013).Crossref, Medline, Google Scholar9 Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood 111(4), 2382–2384 (2008).Crossref, Medline, CAS, Google Scholar10 Kantarjian H, Oki Y, Garcia-Manero G et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109(1), 52–57 (2007).Crossref, Medline, CAS, Google Scholar11 Derissen EJ, Beijnen JH, Schellens JH. Concise drug review: azacitidine and decitabine. Oncologist 18(5), 619–624 (2013).Crossref, Medline, CAS, Google Scholar12 Yang AS, Doshi KD, Choi SW et al. DNA methylation changes after 5-aza-2′-deoxycytidine therapy in patients with leukemia. Cancer Res. 66(10), 5495–5503 (2006).Crossref, Medline, CAS, Google Scholar13 Chuang JC, Yoo CB, Kwan JM et al. Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine. Mol. Cancer Ther. 4(10), 1515–1520 (2005).Crossref, Medline, CAS, Google Scholar14 Qin T, Youssef EM, Jelinek J et al. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin. Cancer. Res. 13(14), 4225–4232 (2007).Crossref, Medline, CAS, Google Scholar15 Kantarjian H, Issa JP, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a Phase III randomized study. Cancer 106(8), 1794–1803 (2006).Crossref, Medline, CAS, Google Scholar16 Steensma DP, Baer MR, Slack JL et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the Alternative Dosing for Outpatient Treatment (ADOPT) trial. J. Clin. Oncol. 27(23), 3842–3848 (2009).Crossref, Medline, CAS, Google Scholar17 Bordoni RE, Feinberg BA, Gilmore JW et al. Hematologic outcomes of myelodysplastic syndromes treatment with hypomethylating agents in community practice. Clin. Lymphoma Myeloma Leuk. 4, 350–354 (2011).Crossref, Google Scholar18 Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J. Clin. Oncol. 28(4), 562–569 (2009).Crossref, Medline, Google Scholar19 Qin T, Castoro R, El Ahdab S et al. Mechanisms of resistance to decitabine in the myelodysplastic syndrome. PLoS ONE 6(8), e23372 (2011).Crossref, Medline, CAS, Google Scholar20 Tsimberidou AM, Said R, Culotta K et al. Phase I study of azacitidine and oxaliplatin in patients with advanced cancers that have relapsed or are refractory to any platinum therapy. Clin. Epigenetics 7(1), 29 (2015).Crossref, Medline, Google Scholar21 Stewart DJ, Issa JP, Kurzrock R et al. Decitabine effect on tumor global DNA methylation and other parameters in a Phase I trial in refractory solid tumors and lymphomas. Clin. Cancer Res. 15(11), 3881–3888 (2009).Crossref, Medline, CAS, Google Scholar22 Chuang JC, Warner SL, Vollmer D et al. S110, a 5-aza-2′-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol. Cancer Ther. 9(5), 1443–1450 (2010).Crossref, Medline, CAS, Google Scholar23 Tellez CS, Grimes MJ, Picchi MA et al. SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome. Int. J. Cancer 135(9), 2223–2231 (2014).Crossref, Medline, CAS, Google Scholar24 Wang Y, Cardenas H, Fang F et al. Epigenetic targeting of ovarian cancer stem cells. Cancer Res. 74(17), 4922–4936 (2014).Crossref, Medline, CAS, Google Scholar25 Issa J-P, Roboz G, Rizzieri D et al. Pharmacokinetic and pharmacodynamic-guided Phase 1 study of the novel hypomethylating drug guadecitabine (SGI-110) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Lancet Oncol. 16(9), 1099–1110 (2015).Crossref, Medline, CAS, Google Scholar26 Garcia Manero G, Ritchie, Walsh K et al. First clinical results of a randomized Phase 2 dose-response study of SGI-110, a novel subcutaneous (SC) hypomethylating agent (HMA), in 102 patients with intermediate (Int) or high risk (HR) myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). Blood 124(21), Abstract 529 (2014).Medline, Google Scholar27 Kantarjian H, Jabbour E, Yee K et al. First clinical results of a randomized Phase 2 study of SGI-110, a novel subcutaneous (SQ) hypomethylating agent (HMA), in adult patients with acute myeloid leukemia (AML). Blood 122(21), Abstract 497 (2013).Crossref, Google Scholar28 Ferraris D, Duvall B, Delahanty G et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J. Med. Chem. 57(6), 2582–2588 (2014).Crossref, Medline, CAS, Google Scholar29 Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J. Clin. Pharmacol. 54(6), 630–639 (2014).Crossref, Medline, CAS, Google Scholar30 Mistry B, Jones M, Kubiak P et al. A Phase 1 study to assess the absolute bioavailability and safety of an oral solution of decitabine in subjects with myelodysplastic syndromes (MDS). Blood 118(21), Abstract 3801 (2011).Crossref, Medline, Google Scholar31 Garcia-Manero G, Gore SD, Cogle C et al. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J. Clin. Oncol. 29(18), 2521–2527 (2011).Crossref, Medline, CAS, Google Scholar32 ClinicalTrials Database: NCT01757535. http://clinicaltrials.gov/ct2/show/NCT.01757535.Google Scholar33 ClinicalTrials Database: NCT01566695. http://clinicaltrials.gov/ct2/show/NCT01566695.Google Scholar34 Lavelle D, Vaitkus K, Ling Y et al. Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. Blood 119(5), 1240–1247 (2012).Crossref, Medline, CAS, Google Scholar35 Oganesian A, Redkar S, Taverna P, Joshi-Hangal R, Azab M. Preclinical data in cynomolgus (cyn) monkeys of ASTX-727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727. Blood 122(21), Abstract 2526 (2013).Crossref, Google Scholar36 ClinicalTrials Database: NCT02103478. http://clinicaltrials.gov/ct2/show/NCT02103478.Google Scholar37 ClinicalTrials Database: NCT02348489. http://clinicaltrials.gov/ct2/show/NCT02348489.Google Scholar38 Fleming G, Ghamande S, Lin Y et al. Clinical epigenetic resensitization of platinum-resistant, recurrent ovarian cancer patients with SGI-110, a novel, second-generation, subcutaneously administered hypomethylating agent (HMA). Cancer Res. 74(20), Abstract 2320 (2014).Medline, Google Scholar39 El-Khoueiry A, Mulcahy MF, Bekaii-Saab T et al. Pharmacodynamic (PD) and pharmacokinetic (PK) results of the second-generation hypomethylating agent, SGI-110, in patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Presented at: American Association for Cancer Research (AACR) 106th Annual Meeting. Philadelphia, PA, USA, 18–22 April 2015.Google Scholar40 Fang F, Munck J, Tang J et al. The novel, small molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer. Clin. Cancer Res. 20(24), 6504–6516 (2014).Crossref, Medline, CAS, Google Scholar41 Covre A, Coral S, Di Giacomo AM, Taverna P, Azab M, Maio M. Epigenetics meets immune checkpoints. Semin. Oncol. 42(3), 506–513 (2015).Crossref, Medline, CAS, Google Scholar42 Coral S, Parisi C, Nicolay HJ et al. Immunomodulatory activity of SGI-110, a 5-aza-2′-deoxycytidine-containing demethylating dinucleotide. Cancer Immunol. Immunother. 62(3), 605–614 (2013).Crossref, Medline, CAS, Google Scholar43 Srivastava P, Paluch BE, Matsuzaki J et al. Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells and xenografts. Leuk. Res. 38(11), 1332–1341 (2014).Crossref, Medline, CAS, Google Scholar44 Srivastava P, Paluch BE, Matsuzaki J et al. Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics 10(3), 237–246 (2015).Crossref, Medline, Google Scholar45 Pulliam N, Taverna P, Lyons J et al. Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient ovarian cancer. Presented at: American Association for Cancer Research (AACR) 106th Annual Meeting. Philadelphia, PA, USA, 18–22 April 2015.Google Scholar46 Muvarak NE, Robert C, Nagaria PK et al. Combination of DNA methyltransferase and PARP inhibitors as a novel therapy strategy for poor prognosis acute myeloid leukemia. Presented at: American Association for Cancer Research (AACR) 106th Annual Meeting. Philadelphia, PA, USA, 18–22 April 2015.Google ScholarFiguresReferencesRelatedDetailsCited ByNew FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applicationsBioorganic & Medicinal Chemistry, Vol. 46Myelodysplastic Syndromes: How to Recognize Risk and Avoid Acute Myeloid Leukemia Transformation23 January 2020 | Current Oncology Reports, Vol. 22, No. 1An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 studyThe Lancet Haematology, Vol. 6, No. 4Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory acute myeloid leukemia6 December 2017 | Cancer, Vol. 124, No. 2Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agentsHematology, Vol. 2017, No. 1Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against MelanomaJournal of Investigative Dermatology, Vol. 137, No. 1Rewiring the solid tumor epigenome for cancer therapy5 August 2016 | Expert Review of Anticancer Therapy, Vol. 16, No. 9DNA Methylation: Basic Principles Vol. 7, No. 7 Follow us on social media for the latest updates Metrics Downloaded 168 times History Published online 6 November 2015 Published in print October 2015 Information© Future Medicine LtdKeywordsazacitidinedecitabineguadecitabinehypomethylating agentsFinancial & competing interests disclosureJN Lowder and P Taverna are employees of Astex Pharmaceuticals. J-PJ Issa is an investigator and research collaborator with Astex Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download
Referência(s)