BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.


:Despite major advances in the treatment of metastatic melanoma, treatment failure is still inevitable in most cases. Manipulation of key epigenetic regulators, including inhibition of Bromodomain and extra-terminal domain (BET) family members impairs cell proliferation in vitro and tumor growth in vivo in different cancers, including melanoma. Here, we investigated the effect of combining the BET inhibitor JQ1 with the BRAF inhibitor Vemurafenib in in vitro and in vivo models of BRAF-mutant melanoma. We performed cytotoxicity and apoptosis assays, and a xenograft mouse model to determine the in vitro and in vivo efficacy of JQ1 in combination with Vemurafenib against BRAF-mutant melanoma cell lines. Further, to investigate the molecular mechanisms underlying the effects of combined treatment, we conducted antibody arrays of in vitro drug-treated cell lines and RNA sequencing of drug-treated xenograft tumors. The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with upregulation of proapoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Collectively, our data provide a rationale for combined BET and BRAF inhibition as a novel strategy for the treatment of melanoma.


Cancer Med


Cancer medicine


Paoluzzi L,Hanniford D,Sokolova E,Osman I,Darvishian F,Wang J,Bradner JE,Hernando E




Has Abstract


2016-06-01 00:00:00










  • Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

    abstract::Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population-based ...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Gupta S,Baxter NN,Hodgson D,Punnett A,Sutradhar R,Pole JD,Nagamuthu C,Lau C,Nathan PC

    更新日期:2020-10-01 00:00:00

  • PD-1 inhibitors for non-small cell lung cancer patients with special issues: Real-world evidence.

    abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) have provided new therapeutic options for non-small cell lung cancer(NSCLC) patients. However, due to concerning increases in immune-related adverse events, clinical trials usually exclude patients with special issues such as viral hepatitis, tuberculosis (Tbc), interstiti...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Byeon S,Cho JH,Jung HA,Sun JM,Lee SH,Ahn JS,Park K,Ahn MJ

    更新日期:2020-04-01 00:00:00

  • Delayed presentation, diagnosis, and psychosocial aspects of male breast cancer.

    abstract:INTRODUCTION:Male breast cancer is uncommon, delay in seeking medical attention often results in late presentation and poor prognosis. METHODS:Retrospective review of a prospectively maintained database was performed. Patients who were still having regular follow-up were contacted for telephone interview. RESULTS:In ...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Co M,Lee A,Kwong A

    更新日期:2020-05-01 00:00:00

  • Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    abstract::Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could ...

    journal_title:Cancer medicine

    pub_type: 杂志文章,随机对照试验


    authors: Boye K,Jacob H,Frikstad KA,Nesland JM,Maelandsmo GM,Dahl O,Nesbakken A,Flatmark K

    更新日期:2016-08-01 00:00:00

  • Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer.

    abstract:OBJECTIVE:CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non-Small Cell Lung Cancer (NSCLC) has not been co...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Arrieta O,Aviles-Salas A,Orozco-Morales M,Hernández-Pedro N,Cardona AF,Cabrera-Miranda L,Barrios-Bernal P,Soca-Chafre G,Cruz-Rico G,Peña-Torres ML,Moncada-Claudio G,Ramirez-Tirado LA

    更新日期:2020-04-01 00:00:00

  • Diagnostic performance of various liquid biopsy methods in detecting colorectal cancer: A meta-analysis.

    abstract::Liquid biopsy is a promising method in detecting colorectal cancer (CRC). However, previous meta-analyses only focused on the diagnostic performance of cell-free DNA (cfDNA). Therefore, we firstly evaluated the overall performance of all liquid biopsy methods. The pooled sensitivities, specificities, diagnostic odds r...

    journal_title:Cancer medicine

    pub_type: 杂志文章,评审


    authors: Zhu Y,Yang T,Wu Q,Yang X,Hao J,Deng X,Yang S,Gu C,Wang Z

    更新日期:2020-08-01 00:00:00

  • Combination chemotherapy plus dasatinib leads to comparable overall survival and relapse-free survival rates as allogeneic hematopoietic stem cell transplantation in Philadelphia positive acute lymphoblastic leukemia.

    abstract:BACKGROUND:The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyro...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Chang J,Douer D,Aldoss I,Vahdani G,Jeong AR,Ghaznavi Z,Zhang S,Yaghmour G,Lee KJ,Weissman A,Akhtari M

    更新日期:2019-06-01 00:00:00

  • Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment.

    abstract::Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Hasumi K,Sugiyama Y,Sakamoto K,Akiyama F

    更新日期:2013-12-01 00:00:00

  • Defining fallopian tube-derived miRNA cancer signatures.

    abstract:BACKGROUND:MicroRNAs have recently emerged as promising circulating biomarkers in diverse cancer types, including ovarian cancer. We utilized conditional, doxycycline-induced fallopian tube (FT)-derived cancer models to identify changes in miRNA expression in tumors and plasma, and further validated the murine findings...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Dejene SB,Ohman AW,Du W,Randhawa D,Bradley A,Yadav N,Elias KM,Dinulescu DM,Setlur SR

    更新日期:2019-11-01 00:00:00

  • Distinctive lung cancer incidence trends among men and women attributable to the period effect in Shanghai: An analysis spanning 42 years.

    abstract:BACKGROUND:Many previous studies reported secular trend of lung cancer incidence and mortality, but little is known about the possible reasons for these trends. METHODS:Data were obtained from Shanghai Cancer Registry. Age-standardized rates were calculated and average annual percent changes (AAPCs) were evaluated by ...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Xie L,Qian Y,Liu Y,Li Y,Jia S,Yu H,Wang C,Qian B,Bao P

    更新日期:2020-04-01 00:00:00

  • Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response: redefining high-risk multiple myeloma in Asian patients.

    abstract::For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with ...

    journal_title:Cancer medicine

    pub_type: 杂志文章,meta分析


    authors: Byun JM,Shin DY,Hong J,Kim I,Kim HK,Lee DS,Koh Y,Yoon SS

    更新日期:2018-03-01 00:00:00

  • CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line.

    abstract::Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several v...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Asai R,Tsuchiya H,Amisaki M,Makimoto K,Takenaga A,Sakabe T,Hoi S,Koyama S,Shiota G

    更新日期:2019-02-01 00:00:00

  • Risk factors and predictors for tumor site origin in metastatic adenocarcinoma of unknown primary site.

    abstract:BACKGROUND:Metastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the surviva...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Li X,Shao Y,Sheng L,Zhu J,Wang Z,Guo K,Sun L

    更新日期:2021-01-06 00:00:00

  • Research progress and design optimization of CAR-T therapy for pancreatic ductal adenocarcinoma.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR-T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR-T therapy for PDAC h...

    journal_title:Cancer medicine

    pub_type: 杂志文章,评审


    authors: Li T,Li H,Li S,Xu S,Zhang W,Gao H,Xu H,Wu C,Wang W,Yu X,Liu L

    更新日期:2019-09-01 00:00:00

  • Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

    abstract::Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chem...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Peixoto RD,Speers C,McGahan CE,Renouf DJ,Schaeffer DF,Kennecke HF

    更新日期:2015-08-01 00:00:00

  • A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors.

    abstract::Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multi...

    journal_title:Cancer medicine

    pub_type: 杂志文章,多中心研究


    authors: Doi T,Lee KH,Kim TM,Ohtsu A,Kim TY,Ikeda M,Yoh K,Gallo Stampino C,Hirohashi T,Suzuki A,Fujii Y,Andrew Williams J,Bang YJ

    更新日期:2016-07-01 00:00:00

  • A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer.

    abstract::Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HE...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Tolaney SM,Jeong J,Guo H,Brock J,Morganstern D,Come SE,Golshan M,Bellon J,Winer EP,Krop IE

    更新日期:2014-04-01 00:00:00

  • Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer.

    abstract::TRC105 is an endoglin-targeting drug that possesses anti-angiogenic and antitumor potential. Analysis of the initial phase I trial of TRC105 demonstrated good tolerability and efficacy in cancer patients. In this report, we analyzed multiple circulating biomarkers at baseline, cycle 2 day 1 (C2D1), and end of study (E...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Liu Y,Starr MD,Brady JC,Dellinger A,Pang H,Adams B,Theuer CP,Lee NY,Hurwitz HI,Nixon AB

    更新日期:2014-06-01 00:00:00

  • Long noncoding RNA RP11-547D24.1 regulates proliferation and migration in papillary thyroid carcinoma: Identification and validation of a novel long noncoding RNA through integrated analysis of TCGA database.

    abstract::Long noncoding RNAs (lncRNAs) are known to be key regulators of numerous biological processes, and substantial evidence supports that abnormal lncRNA expression plays a significant role in tumorigenesis and tumor progression. However, the mechanism by which lncRNAs function in thyroid carcinoma are still unclear. To i...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Guo K,Chen L,Wang Y,Qian K,Zheng X,Sun W,Sun T,Wu Y,Wang Z

    更新日期:2019-06-01 00:00:00

  • Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.

    abstract:BACKGROUND:Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biolog...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Xia Z,Su YR,Petersen P,Qi L,Kim AE,Figueiredo JC,Lin Y,Nan H,Sakoda LC,Albanes D,Berndt SI,Bézieau S,Bien S,Buchanan DD,Casey G,Chan AT,Conti DV,Drew DA,Gallinger SJ,Gauderman WJ,Giles GG,Gruber SB,Gunter MJ,

    更新日期:2020-05-01 00:00:00

  • Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations.

    abstract::Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), con...

    journal_title:Cancer medicine

    pub_type: 杂志文章,评审


    authors: Mir MA,Kochuparambil ST,Abraham RS,Rodriguez V,Howard M,Hsu AP,Jackson AE,Holland SM,Patnaik MM

    更新日期:2015-04-01 00:00:00

  • High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia.

    abstract:INTRODUCTION:Recent advances in genetic analysis have led to the discovery of novel genetic subtypes of precursor B-cell acute lymphoblastic leukemia (B-ALL) with prognostic relevance. In this study, we studied a cohort of pediatric B-ALL patients to retrospectively determine the incidence of patients harboring novel g...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Lee JW,Kim Y,Cho B,Kim S,Jang PS,Lee J,Cho H,Lee GD,Chung NG,Kim M

    更新日期:2020-07-01 00:00:00

  • MUC1 as a target for CAR-T therapy in head and neck squamous cell carinoma.

    abstract::The modification of chimeric antigen receptor (CAR) endowing T cells with tumor-specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR-T therapy....

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Mei Z,Zhang K,Lam AK,Huang J,Qiu F,Qiao B,Zhang Y

    更新日期:2020-01-01 00:00:00

  • External beam radiotherapy for prostate cancer: What are the current research trends and hotspots?

    abstract:BACKGROUND:The external beam radiotherapy (EBRT) applied for prostate cancer (PCa) has been one of the most important and hottest research fields over recent decades. This study aimed to explore the research hotspots of EBRT in PCa and help the researchers have a clear and intuitive reference basis for later researches...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Li R,Liu X,Yang B,Qiu J

    更新日期:2021-01-21 00:00:00

  • Long noncoding RNA MSC-AS1 promotes hepatocellular carcinoma oncogenesis via inducing the expression of phosphoglycerate kinase 1.

    abstract:BACKGROUND AND OBJECTIVES:Increasing studies report that lncRNAs are dysregulated in hepatocellular carcinoma (HCC), which might function as significant diagnostic biomarkers of HCC. LncRNA MSC-AS1 has been newly discovered in several cancers. However, its biological effect in HCC remains to be clearly elucidated. The ...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Cao C,Zhong Q,Lu L,Huang B,Li J,Meng L,Wei H

    更新日期:2020-07-01 00:00:00

  • LncRNA NEAT1 knockdown attenuates autophagy to elevate 5-FU sensitivity in colorectal cancer via targeting miR-34a.

    abstract:BACKGROUNDS:Colorectal carcinoma (CRC) is a common malignant tumor. Increasing evidences indicated that CRC showed a resistance to 5-fluorouracil (5-FU) and further resulted in a poor prognosis. In this study, we aim to investigate the effect of long noncoding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Liu F,Ai FY,Zhang DC,Tian L,Yang ZY,Liu SJ

    更新日期:2020-02-01 00:00:00

  • Development and validation of a simple risk model to predict major cancers for patients with nonalcoholic fatty liver disease.

    abstract:OBJECTIVE:To recognize risk factors and build up and validate a simple risk model predicting 8-year cancer events after nonalcoholic fatty liver disease (NAFLD). METHODS:This was a retrospective cohort study. Patients with NAFLD (n = 5561) were randomly divided into groups: training (n = 1254), test (n = 627), evaluat...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Wei Z,Ren Z,Hu S,Gao Y,Sun R,Lv S,Yang G,Yu Z,Kan Q

    更新日期:2020-02-01 00:00:00

  • TGF-β-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression.

    abstract::Previous studies indicated that transforming growth factor (TGF)-β-mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF-β-mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, cocult...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Wu DM,Deng SH,Liu T,Han R,Zhang T,Xu Y

    更新日期:2018-10-01 00:00:00

  • MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

    abstract::Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in...

    journal_title:Cancer medicine

    pub_type: 杂志文章,评审


    authors: Shea A,Harish V,Afzal Z,Chijioke J,Kedir H,Dusmatova S,Roy A,Ramalinga M,Harris B,Blancato J,Verma M,Kumar D

    更新日期:2016-08-01 00:00:00

  • Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status.

    abstract::Gastric cancer (GC) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expressi...

    journal_title:Cancer medicine

    pub_type: 杂志文章


    authors: Wang L,Zhang Q,Ni S,Tan C,Cai X,Huang D,Sheng W

    更新日期:2018-06-01 00:00:00