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Yan Zeng

Bio: Yan Zeng is an academic researcher from Indiana University – Purdue University Indianapolis. The author has contributed to research in topics: Cancer & Decitabine. The author has an hindex of 3, co-authored 3 publications receiving 305 citations.

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TL;DR: The results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS.
Abstract: Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P < 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine-cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P < 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P < 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS.

326 citations

Journal ArticleDOI
TL;DR: Low-dose D alters DNA methylation restoring sensitivity to Cp in patients with heavily pre-treated OC, resulting in a high RR and prolonged PFS, and is positively correlated with PFS.
Abstract: 5011 Background: Aberrant DNA methylation is a hallmark of cancer. Preclinical studies showed that hypomethylating agents reverse Pt resistance, supporting testing low dose decitabine (D) combined ...

11 citations

Journal ArticleDOI
TL;DR: This phase I/II trial evaluates tolerability and efficacy of B combined with pegylated liposomal doxorubicin hydrochloride in platinum-resistant OC to determine the maximum-tolerated dose and response rate to D+B.
Abstract: 5541^ Background: The triple PDGFRα/β, VEGFR1-3, FGFR1-3 angiokinase inhibitor BIBF 1120 (B) is active in ovarian cancer (OC). This phase I/II trial evaluates tolerability and efficacy of B combine...

4 citations


Cited by
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Journal ArticleDOI
27 Aug 2015-Cell
TL;DR: In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.

1,181 citations

Journal ArticleDOI
TL;DR: It is shown that 5-aza-2'-deoxycytidine treatment not only reactivates genes but decreases the overexpression of genes, many of which are involved in metabolic processes regulated by c-MYC.

882 citations

Journal ArticleDOI
TL;DR: As epigenetic drugs target the epigenome as a whole, these true 'genomic medicines' lessen the need for precision approaches to individualized therapies.
Abstract: Next-generation sequencing has revealed that more than 50% of human cancers harbour mutations in enzymes that are involved in chromatin organization. Tumour cells not only are activated by genetic and epigenetic alterations, but also routinely use epigenetic processes to ensure their escape from chemotherapy and host immune surveillance. Hence, a growing emphasis of recent drug discovery efforts has been on targeting the epigenome, including DNA methylation and histone modifications, with several new drugs being tested and some already approved by the US Food and Drug Administration (FDA). The future will see the increasing success of combining epigenetic drugs with other therapies. As epigenetic drugs target the epigenome as a whole, these true 'genomic medicines' lessen the need for precision approaches to individualized therapies.

837 citations

Journal ArticleDOI
TL;DR: This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015 and aims to reduce incidence and improve outcomes for women with this disease.
Abstract: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.

801 citations

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TL;DR: Epigenetic therapies are one standard of care for a preleukemic disorder and form of lymphoma and the application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route.
Abstract: SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome. Epigenetic therapies, in which the goal is to reverse these changes, are now one standard of care for a preleukemic disorder and form of lymphoma. The application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route.

771 citations