Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non Small Cell Lung Cancer

By R. Juergens, J. Wrangle, F. Vendetti, S. Murphy, Ming Zhao, B. Coleman, R. Sebree, Kristen Rodgers, C. Hooker, N. Franco and 9 more. Cancer Discovery, 2011

619 citations recorded by the source corpus.

Epigenetic alterations are strongly associated with cancer development. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non-small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI: 3.8–9.2), comparing favorably with existing therapeutic options. Demethylation of a set of four epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients, and was associated with improved progression-free (p=0.034) and overall survival (p=0.035). Four of 19 patients had major objective responses to subsequent anti-cancer therapies given immediately following epigenetic therapy.

Subfields: Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4ba4f4b9d190b312191c23da888ccbfef4bca621

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Citations in the corpus

Combination therapy in combating cancer (2017, background): “4 months) and progression-free survival compared to the current therapeutics available for this type of cancer [115, 116].”
Transient Low Doses of DNA Demethylating Agents Exert Durable Anti-tumor Effects on Hematological and Epithelial Tumor Cells (2012, background): “Moreover, it is especially appealing to consider that DAC and AZA might sensitize tumor cells to other drugs, as is suggested by Juergens et al. (2011), that target the oncogenic pathways we have shown to be altered and allow use of reduced, less toxic, doses for these other agents.”
Epigenetic Determinants of Cancer. (2016, background): “Closely related to this, recently completed clinical trials in 65 patients with advanced lung cancer, the deadliest of all human cancers, show promise that these approaches can, in a small subset of patients, induce robust, durable responses (Juergens et al. 2011).”
Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer (2014, background): “…clinical trials have been initiated to investigate the possibility of extending their utilization to solid tumors, such as ovarian and lung cancers, either alone or in combination with other drugs (Azad et al., 2013; Juergens et al., 2011; Li et al., 2014; Matei et al., 2012;Wrangle et al., 2013).”
Cancer Genetics and Epigenetics: Two Sides of the Same Coin? (2012, background): “The presence of multiple genetic and epigenetic aberrations within a cancer suggests that effective cancer therapies will be most beneficial when combined with epigenetic and/or other anti-cancer strategies such as standard chemotherapy (Juergens et al., 2011; Matei and Nephew, 2010).”
Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses (2015, positive): “IRF7 is frequently promoter DNA hypermethylated in cancer and the associated low basal expression can be reversed by Aza in squamous NSCLC (Wrangle et al., 2013).”