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Melanoma: HELP
Articles by Bin Zheng
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, Bin Zheng wrote the following 11 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Targeted inhibition of BRAF kinase: opportunities and challenges for therapeutics in melanoma. 2012

Pérez-Lorenzo, Rolando / Zheng, Bin. ·Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA. ·Biosci Rep · Pubmed #21981139.

ABSTRACT: Malignant melanoma is the most aggressive form of skin cancer and its incidence has increased dramatically in the last two decades. Even with a high rate of success in the treatment of early stages of this malignancy, currently there are no effective strategies for the treatment of advanced metastatic melanoma. Much effort has been put into the use of different target-specific drugs, among which BRAF kinase-specific small-molecule inhibitors have rendered promising results as therapeutic agents in metastatic melanoma. Nonetheless, some side effects, such as development of SCC (squamous cell carcinoma), as well as tumour resistance and recurrence, are common limitations of this therapeutic strategy. The use of combination treatments in which different regulatory pathways or the immunological response are targeted seems to be a promising tool for the future success of melanoma therapeutics.

2 Article SIRT6 haploinsufficiency induces BRAF 2018

Strub, Thomas / Ghiraldini, Flavia G / Carcamo, Saul / Li, Man / Wroblewska, Aleksandra / Singh, Rajendra / Goldberg, Matthew S / Hasson, Dan / Wang, Zichen / Gallagher, Stuart J / Hersey, Peter / Ma'ayan, Avi / Long, Georgina V / Scolyer, Richard A / Brown, Brian / Zheng, Bin / Bernstein, Emily. ·Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA. · Department of Genetics and Genomic Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Department of Pathology, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Centenary Institute, Camperdown NSW 2050, The University of Sydney, Sydney, Australia. · Melanoma Institute Australia, Wollstonecraft NSW 2065, The University of Sydney, Sydney, Australia. · Sydney Medical School, University of Sydney, Sydney, NSW, 2050, Australia. · Royal North Shore Hospital, Sydney, NSW, 2065, Australia. · Royal Prince Alfred Hospital, Sydney, NSW, 2050, Australia. · Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. · Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. emily.bernstein@mssm.edu. · Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. emily.bernstein@mssm.edu. · Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. emily.bernstein@mssm.edu. ·Nat Commun · Pubmed #30143629.

ABSTRACT: While multiple mechanisms of BRAF

3 Article Supplementing Cancer? 2018

Swanson, Kenneth D / Zheng, Bin. ·Brain Tumor Center and Neuro-Oncology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: kswanson@bidmc.harvard.edu. · Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: bin.zheng@cbrc2.mgh.harvard.edu. ·Mol Cell · Pubmed #29547718.

ABSTRACT: In this issue of Molecular Cell, Lin et al. (2018) report that chondroitin-4-sulfate, which is found in a common supplement meant to alleviate degenerative joint disorders, promotes the growth of BRAF V600E mutant melanoma. This study not only has implications for patient care but also sheds light on a novel mechanism for regulating phosphoinositide 3-kinase signaling.

4 Article Phenformin Inhibits Myeloid-Derived Suppressor Cells and Enhances the Anti-Tumor Activity of PD-1 Blockade in Melanoma. 2017

Kim, Sun Hye / Li, Man / Trousil, Sebastian / Zhang, Yaqing / Pasca di Magliano, Marina / Swanson, Kenneth D / Zheng, Bin. ·Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. · Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA. · Department of Neurology, Brain Tumor Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. · Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. Electronic address: bin.zheng@cbrc2.mgh.harvard.edu. ·J Invest Dermatol · Pubmed #28433543.

ABSTRACT: Biguanides, such as the diabetes therapeutics metformin and phenformin, have shown antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells in spleens of tumor-bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in granulocytic myeloid-derived suppressor cells, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin. Co-treatment of phenformin enhances the effect of anti-PD-1 antibody therapy on inhibiting tumor growth in the BRAF V600E/PTEN-null melanoma mouse model. Combination of phenformin and anti PD-1 cooperatively induces CD8

5 Article Phenformin Enhances the Efficacy of ERK Inhibition in NF1-Mutant Melanoma. 2017

Trousil, Sebastian / Chen, Shuang / Mu, Chan / Shaw, Fiona M / Yao, Zhan / Ran, Yuping / Shakuntala, Tiwari / Merghoub, Taha / Manstein, Dieter / Rosen, Neal / Cantley, Lewis C / Zippin, Jonathan H / Zheng, Bin. ·Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. · Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA; Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. · Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. · Department of Dermatology, Weill Cornell Medical College, New York, New York, USA. · Division of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. · Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. · Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, New York, USA. · Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. Electronic address: bin.zheng@cbrc2.mgh.harvard.edu. ·J Invest Dermatol · Pubmed #28143781.

ABSTRACT: Inactivation of the tumor suppressor neurofibromin 1 (NF1) presents a newly characterized melanoma subtype, for which currently no targeted therapies are clinically available. Preclinical studies suggest that extracellular signal-regulated kinase (ERK) inhibitors are likely to provide benefit, albeit with limited efficacy as a single agent; therefore, there is a need for rationally designed combination therapies. Here, we evaluate the combination of the ERK inhibitor SCH772984 and the biguanide phenformin. A combination of both compounds showed potent synergy in cell viability assays and cooperatively induced apoptosis. Treatment with both drugs was required to fully suppress mechanistic target of rapamycin signaling, a known effector of NF1 loss. Mechanistically, SCH772984 increased the oxygen consumption rate, indicating that these cells relied more on oxidative phosphorylation upon treatment. Consistently, SCH772984 increased expression of the mitochondrial transcriptional coactivator peroxisome proliferator-activated receptor gamma, coactivator 1-α. In contrast, cotreatment with phenformin, an inhibitor of complex I of the respiratory chain, decreased the oxygen consumption rate. SCH772984 also promoted the expansion of the H3K4 demethylase KDM5B (also known as JARID1B)-positive subpopulation of melanoma cells, which are slow-cycling and treatment-resistant. Importantly, phenformin suppressed this KDM5B-positive population, which reduced the emergence of SCH772984-resistant clones in long-term cultures. Our results warrant the clinical investigation of this combination therapy in patients with NF1 mutant melanoma.

6 Article Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma. 2016

Shen, Che-Hung / Kim, Sun Hye / Trousil, Sebastian / Frederick, Dennie T / Piris, Adriano / Yuan, Ping / Cai, Li / Gu, Lei / Li, Man / Lee, Jung Hyun / Mitra, Devarati / Fisher, David E / Sullivan, Ryan J / Flaherty, Keith T / Zheng, Bin. ·Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. · Department of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. · Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. ·Nat Med · Pubmed #27500726.

ABSTRACT: The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extended survival in patients with melanoma who bear tumors that express mutations encoding BRAF proteins mutant at Val600, but a vast majority of these patients develop drug resistance. Here we show that loss of stromal antigen 2 (STAG2) or STAG3, which encode subunits of the cohesin complex, in melanoma cells results in resistance to BRAFi. We identified loss-of-function mutations in STAG2, as well as decreased expression of STAG2 or STAG3 proteins in several tumor samples from patients with acquired resistance to BRAFi and in BRAFi-resistant melanoma cell lines. Knockdown of STAG2 or STAG3 expression decreased sensitivity of BRAF(Val600Glu)-mutant melanoma cells and xenograft tumors to BRAFi. Loss of STAG2 inhibited CCCTC-binding-factor-mediated expression of dual specificity phosphatase 6 (DUSP6), leading to reactivation of mitogen-activated protein kinase (MAPK) signaling (via the MAPKs ERK1 and ERK2; hereafter referred to as ERK). Our studies unveil a previously unknown genetic mechanism of BRAFi resistance and provide new insights into the tumor suppressor function of STAG2 and STAG3.

7 Article Addicted to AA (Acetoacetate): A Point of Convergence between Metabolism and BRAF Signaling. 2015

Trousil, Sebastian / Zheng, Bin. ·Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA. · Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bin.zheng@cbrc2.mgh.harvard.edu. ·Mol Cell · Pubmed #26253025.

ABSTRACT: In this issue Kang et al. (2015) show that oncogenic BRAF(V600E) stimulates expression of ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA lyase and promotes the formation of the ketone body acetoacetate, which subsequently enhances BRAF(V600E)/MEK/ERK signaling.

8 Article Metabolic vulnerability in melanoma: a ME2 (me too) story. 2015

Zheng, Bin / Fisher, David E. ·Department of Dermatology, Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Dermatology, Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: dfisher3@mgh.harvard.edu. ·J Invest Dermatol · Pubmed #25666673.

ABSTRACT: Metabolic reprograming is a hallmark of cancer and might represent an Achilles' heel in cancer cells. The study by Chang et al. in this issue highlights a critical role of mitochondrial malic enzyme 2 (ME2) in melanoma progression. Targeting ME2 could be an effective approach to inhibit melanoma cell proliferation and tumor growth.

9 Article p53 Protein-mediated regulation of phosphoglycerate dehydrogenase (PHGDH) is crucial for the apoptotic response upon serine starvation. 2015

Ou, Yang / Wang, Shang-Jui / Jiang, Le / Zheng, Bin / Gu, Wei. ·From the Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and. · the Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129. · From the Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and wg8@columbia.edu. ·J Biol Chem · Pubmed #25404730.

ABSTRACT: Although p53 is frequently mutated in human cancers, about 80% of human melanomas retain wild-type p53. Here we report that PHGDH, the key metabolic enzyme that catalyzes the rate-limiting step of the serine biosynthesis pathway, is a target of p53 in human melanoma cells. p53 suppresses PHGDH expression and inhibits de novo serine biosynthesis. Notably, upon serine starvation, p53-mediated cell death is enhanced dramatically in response to Nutlin-3 treatment. Moreover, PHGDH has been found recently to be amplified frequently in human melanomas. We found that PHGDH overexpression significantly suppresses the apoptotic response, whereas RNAi-mediated knockdown of endogenous PHGDH promotes apoptosis under the same treatment. These results demonstrate an important role of p53 in regulating the serine biosynthesis pathway through suppressing PHGDH expression and reveal serine deprivation as a novel approach to sensitize p53-mediated apoptotic responses in human melanoma cells.

10 Article A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms. 2014

Perez-Lorenzo, Rolando / Gill, Kamraan Z / Shen, Che-Hung / Zhao, Feng X / Zheng, Bin / Schulze, Hans-Joachim / Silvers, David N / Brunner, Georg / Horst, Basil A. ·Department of Dermatology, Columbia University Medical Center, New York, New York, USA. · Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. · Institute for Cancer Genetics, Columbia University, New York, New York, USA. · Department of Dermatology, Fachklinik Hornheide at University Muenster, Muenster, Germany. · Department of Cancer Research, Fachklinik Hornheide at University Muenster, Muenster, Germany. · Department of Dermatology, Columbia University Medical Center, New York, New York, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address: bh2179@cumc.columbia.edu. ·J Invest Dermatol · Pubmed #24288008.

ABSTRACT: The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

11 Article Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. 2013

Yuan, Ping / Ito, Koichi / Perez-Lorenzo, Rolando / Del Guzzo, Christina / Lee, Jung Hyun / Shen, Che-Hung / Bosenberg, Marcus W / McMahon, Martin / Cantley, Lewis C / Zheng, Bin. ·Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129. ·Proc Natl Acad Sci U S A · Pubmed #24145418.

ABSTRACT: Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. The energy-sensing AMP-activated protein kinase (AMPK) is known to be a major cellular target of biguanides. Based on our discovery of cross-talk between the AMPK and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) signaling pathways, we investigated the antitumor effects of combining phenformin with a BRAF inhibitor PLX4720 on the proliferation of BRAF-mutated melanoma cells in vitro and on BRAF-driven tumor growth in vivo. Cotreatment of BRAF-mutated melanoma cell lines with phenformin and PLX4720 resulted in synergistic inhibition of cell viability, compared with the effects of the single agent alone. Moreover, treatment with phenformin significantly delayed the development of resistance to PLX4720 in cultured melanoma cells. Biochemical analyses showed that phenformin and PLX4720 exerted cooperative effects on inhibiting mTOR signaling and inducing apoptosis. Noticeably, phenformin selectively targeted subpopulations of cells expressing JARID1B, a marker for slow cycling melanoma cells, whereas PLX4720 selectively targeted JARID1B-negative cells. Finally, in contrast to their use as single agents, the combination of phenformin and PLX4720 induced tumor regression in both nude mice bearing melanoma xenografts and in a genetically engineered BRAF(V600E)/PTEN(null)-driven mouse model of melanoma. These results strongly suggest that significant therapeutic advantage may be achieved by combining AMPK activators such as phenformin with BRAF inhbitors for the treatment of melanoma.