Safety and efficacy of azacitidine in myelodysplastic syndromes

Vigil, Carlos Enrique; Martín‐Santos, Taida

doi:10.2147/dddt.s3143

Cited by 33 publications

(28 citation statements)

References 47 publications

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“…Thus, patients with tumors harboring epigenetic alterations could benefit from treatment with demethylating agents. 5-Azacytidine is a demethylating agent that inhibits DNA methyltransferase 1 in replicating cells [100] and has recently been shown to prolong survival and improve quality of life in patients with myelodysplastic syndromes, while maintaining a favorable adverse-effect profile [101]. Prospective studies in NSCLC with promising results are ongoing [102].…”

Section: Cyclin-dependent Kinase Inhibitorsmentioning

confidence: 99%

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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Non-small-cell lung cancer (NSCLC) is among the most frequently diagnosed malignancy and a leading cause for cancer mortality worldwide. Despite various efforts, practical prognostic and predictive markers are still few. We review recent findings concerning the cell cycle in NSCLC and discuss prognostic and predictive aspects as well as the challenge of targeted therapeutic approaches. Deregulation of the cell cycle is a common event in NSCLC. Usually, several defects of cell cycle regulation are concomitant and have a cumulative adverse effect on prognosis. Therefore, analysis of a variety of interacting molecules is desirable for adequate deductions. Immunohistochemical interpretations should include the subcellular staining localization, since this can reflect the functional properties of a protein. Overexpression of cyclins, especially D-type cyclins, has repeatedly been associated with poor prognosis in NSCLC. Predictive data is less conclusive; however, loss of the expression of cyclin-dependent kinase inhibitors seems to correlate with sensitivity to antiproliferative drugs. Various inhibitors of Aurora kinases are currently being evaluated regarding their potential as targeted therapies in NSCLC. In conclusion, the cell cycle offers several prognostic, predictive and therapeutic possibilities in NSCLC, many still developmental. Progress in this field has the potential to improve the current scenario for NSCLC patients.

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Section: Cyclin-dependent Kinase Inhibitorsmentioning

confidence: 99%

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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“…Demethylation is known to reactivate the expression of many genes silenced in cultured tumour cells [82]. While high doses of DNMT inhibitors can inhibit DNA synthesis and eventually lead to cell death by cytotoxicity, administration of low doses of these drugs over a prolonged period has a therapeutic effect [188][189][190][191]. In fact, the United States Food and Drug Administration has approved the DNMT inhibitors, 5-azacytidine and its derivative 5-aza-2′-deoxycytidine (decitabine), for therapy of patients with solid tumours, myelodysplastic syndrome (which can lead to the development of acute leukemia) and myelogenous leukemia [192].…”

Section: Therapeutic Applicationsmentioning

confidence: 99%

Breaking the Silence: The Interplay Between Transcription Factors and DNA Methylation

Baron¹

2012

Methylation - From DNA, RNA and Histones to Diseases and Treatment

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“…The Kaplan-Meier estimates for OS and progression-free survival between the two groups did not show clear evidence of a favorable outcome for either group, and there were no marked differences in toxic effects and other complications between the two groups [Vigil et al 2010].…”

Section: Role Of Azacitidine In the Transplant Settingmentioning

confidence: 76%

Azacitidine in the management of patients with myelodysplastic syndromes

Khan

Pathe

Fazal

et al. 2012

Therapeutic Advances in Hematology

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoeitic disorders characterized by ineffective hematopoiesis and potential transformation to acute myeloid leukemia (AML). For decades, the mainstay of treatment for MDS was supportive care, including transfusion of blood products and growth factors. Further understanding of disease biology led to the discovery of a high prevalence of hypermethylation of tumor suppressor genes in high-risk MDS and secondary leukemias. Hence, the role of irreversible DNA methlytransferase inhibitors such as azacitidine was investigated with promising outcomes in the treatment of MDS. Azacitidine was initially approved in the USA by the Food and Drug Administration (FDA) in 2004 for the treatment of all subtypes of MDS and was granted expanded approval in 2009 to reflect new overall survival data demonstrated in the AZA-001 study of patients with higher-risk MDS. Azacitidine has demonstrated significant and clinically meaningful prolongation of survival in higher-risk patients with MDS and has changed the natural history of these disorders. The agent maintains a relatively safe toxicity profile, even in older patients. The role of azacitidine has been explored in the treatment of AML and chronic myelomonocytic leukemia and has also been studied in the peritransplant setting. Azacitidine has been combined with other novel agents such as lenalidomide, histone deacetylase inhibitors and growth factors in the hope of achieving improved outcomes. Currently, both intravenous and subcutaneous forms of azacitidine are approved for use in the USA with the oral form being granted fast track status by the FDA.

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Safety and efficacy of azacitidine in myelodysplastic syndromes

Cited by 33 publications

References 47 publications

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Breaking the Silence: The Interplay Between Transcription Factors and DNA Methylation

Azacitidine in the management of patients with myelodysplastic syndromes

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