Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.

abstract：UNLABELLED:Adenoid cystic carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with a bleak prognosis for which therapeutic targets are unavailable. We used RNA sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to ...

journal_title：Cancer discovery

authors： Brayer KJ,Frerich CA,Kang H,Ness SA

更新日期：2016-02-01 00:00:00

abstract：:CD14+CD16-HLA-DRhi monocyte frequency was linked to response to anti-PD-1 in patients with melanoma. ...

journal_title：Cancer discovery

authors：

更新日期：2018-03-01 00:00:00

abstract：:DNA repair deficiencies are common among cancer cells and represent a potential vulnerability that might be exploited by targeting compensatory repair pathways. However, the identification of synthetically lethal combinations of DNA repair defects, although of significant clinical relevance, has been somewhat anecdota...

journal_title：Cancer discovery

authors： Hemann MT

更新日期：2014-05-01 00:00:00

abstract：:Results from a randomized phase II study indicate that adding the experimental antibody IMAB362, which targets the tight junction protein claudin18.2, to standard chemotherapy is more effective than chemotherapy alone in previously untreated patients with advanced gastric cancer. IMAB362 extended progression-free and ...

journal_title：Cancer discovery

authors：

更新日期：2016-08-01 00:00:00

abstract：:In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infu...

journal_title：Cancer discovery

authors：

更新日期：2017-02-01 00:00:00

abstract：:Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of ...

journal_title：Cancer discovery

authors： Goyal L,Saha SK,Liu LY,Siravegna G,Leshchiner I,Ahronian LG,Lennerz JK,Vu P,Deshpande V,Kambadakone A,Mussolin B,Reyes S,Henderson L,Sun JE,Van Seventer EE,Gurski JM Jr,Baltschukat S,Schacher-Engstler B,Barys L,Stam

更新日期：2017-03-01 00:00:00

abstract：:Oncogenic KRAS (KRAS*) is a key tumor maintenance gene in pancreatic ductal adenocarcinoma (PDAC), motivating pharmacologic targeting of KRAS* and its effectors. Here, we explored mechanisms involving the tumor microenvironment (TME) as a potential basis for resistance to targeting KRAS*. Using the inducible KrasG12D;...

journal_title：Cancer discovery

authors： Hou P,Kapoor A,Zhang Q,Li J,Wu CJ,Li J,Lan Z,Tang M,Ma X,Ackroyd JJ,Kalluri R,Zhang J,Jiang S,Spring DJ,Wang YA,DePinho RA

更新日期：2020-07-01 00:00:00

abstract：:Presenting data on 50 of 55 patients with advanced TRK fusion-positive tumors, researchers reported that 76% of patients responded to the selective pan-TRK inhibitor larotrectinib, and 12% of patients experienced complete responses; 93% of responders remain on therapy. The targeted therapy was well tolerated, with jus...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 00:00:00

abstract：:Circadian rhythms integrate many physiological pathways, helping organisms to align the timing of various internal processes to daily cycles in the external environment. Disrupted circadian rhythmicity is a prominent feature of modern society, and has been designated as a probable carcinogen. Here, we review multiple ...

journal_title：Cancer discovery

authors： Pariollaud M,Lamia KA

更新日期：2020-10-01 00:00:00

abstract：:A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：:Findings from a phase I study suggest that delivering high concentrations of the chemotherapy 5-FU directly to brain tumors via the retroviral vector vocimagene amiretrorepvec, or Toca 511, may benefit patients with recurrent high-grade glioma. This investigational treatment was well tolerated and induced robust, dura...

journal_title：Cancer discovery

authors：

更新日期：2018-01-01 00:00:00

abstract：:Based on the results of two large international randomized trials, the FDA approved the anti-PD-L1 agent atezolizumab in October. It is the first PD-L1 inhibitor approved for use in patients with metastatic non-small cell lung cancer that has advanced in spite of treatment with platinum-based chemotherapy. ...

journal_title：Cancer discovery

authors：

更新日期：2016-12-01 00:00:00

abstract：:A new study of zebrafish may explain why only certain skin cells grow into tumors. Besides melanoma-promoting mutations, these cells express key neural crest genes, such as crestin and sox10, that induce regression to an embryonic state. They also bear epigenetic changes that might amplify expression of these genes. ...

journal_title：Cancer discovery

authors： Leslie M

更新日期：2016-04-01 00:00:00

abstract：:The overall budget for the NCI has increased by about $1 billion since 2009, yet the payline for new R01 grants has continued to decrease, largely due to an influx of R01 grant applications. Researchers, troubled by this trend, are wondering why the NCI is receiving so many more applications and what can be done to im...

journal_title：Cancer discovery

authors：

更新日期：2019-05-01 00:00:00

abstract：UNLABELLED:Many epithelial cancers are associated with chronic inflammation. However, the features of inflammation that are procarcinogenic are not fully understood. Regulatory T cells (Treg) typically restrain overt inflammatory responses and maintain intestinal immune homeostasis. Their immune-suppressive activity ca...

journal_title：Cancer discovery

authors： Geis AL,Fan H,Wu X,Wu S,Huso DL,Wolfe JL,Sears CL,Pardoll DM,Housseau F

更新日期：2015-10-01 00:00:00

abstract：:Adding entinostat to exemestane improves survival in women with ER(+) advanced breast cancer. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：:Agonistic antibodies targeting CD137 have been clinically unsuccessful due to systemic toxicity. Because conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigens, we exploited extracellular adenosine triphosphate (exATP), which is a hallmark of ...

journal_title：Cancer discovery

authors： Kamata-Sakurai M,Narita Y,Hori Y,Nemoto T,Uchikawa R,Honda M,Hironiwa N,Taniguchi K,Shida-Kawazoe M,Metsugi S,Miyazaki T,Wada NA,Ohte Y,Shimizu S,Mikami H,Tachibana T,Ono N,Adachi K,Sakiyama T,Matsushita T,Kadono

更新日期：2020-08-25 00:00:00

abstract：:A comprehensive analysis of 1,122 diffuse glioma samples from The Cancer Genome Atlas has revealed two new subtypes of this common brain cancer, with molecular and clinical features that diverge from the norm. The study findings also support the use of DNA methylation profiles to improve glioma classification and trea...

journal_title：Cancer discovery

authors： Poh A

更新日期：2016-04-01 00:00:00

abstract：:Oncogenes induce premature S phase, resulting in replication-transcription conflicts and replication stress. ...

journal_title：Cancer discovery

authors：

更新日期：2018-04-01 00:00:00

abstract：:A phase III trial testing nivolumab to treat advanced melanoma was stopped early due to improved overall survival compared with standard chemotherapy. ...

journal_title：Cancer discovery

authors：

更新日期：2014-09-01 00:00:00

abstract：:Targeting the dysregulated BRAF-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRAF and MEK, resistance develops often involving nongenomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in patients ...

journal_title：Cancer discovery

authors： Zawistowski JS,Bevill SM,Goulet DR,Stuhlmiller TJ,Beltran AS,Olivares-Quintero JF,Singh D,Sciaky N,Parker JS,Rashid NU,Chen X,Duncan JS,Whittle MC,Angus SP,Velarde SH,Golitz BT,He X,Santos C,Darr DB,Gallagher K,Gr

更新日期：2017-03-01 00:00:00

abstract：UNLABELLED:Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy, and its molecular basis is poorly understood. We previously demonstrated that opioid binding protein cell adhesion molecule (OPCML) was frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppress...

journal_title：Cancer discovery

authors： McKie AB,Vaughan S,Zanini E,Okon IS,Louis L,de Sousa C,Greene MI,Wang Q,Agarwal R,Shaposhnikov D,Wong JL,Gungor H,Janczar S,El-Bahrawy M,Lam EW,Chayen NE,Gabra H

更新日期：2012-02-01 00:00:00

abstract：:The FDA authorized 23andMe to market the first direct-to-consumer test to check for three BRCA1/2 mutations associated with a higher risk of developing breast, ovarian, and prostate cancers. The mutations are most commonly found in about 2% of women of Ashkenazi Jewish descent. ...

journal_title：Cancer discovery

authors：

更新日期：2018-05-01 00:00:00

abstract：UNLABELLED:Despite the impressive clinical activity of the second-generation antiandrogens enzalutamide and ARN-509 in patients with prostate cancer, acquired resistance invariably emerges. To identify the molecular mechanisms underlying acquired resistance, we developed and characterized cell lines resistant to ARN-50...

journal_title：Cancer discovery

authors： Joseph JD,Lu N,Qian J,Sensintaffar J,Shao G,Brigham D,Moon M,Maneval EC,Chen I,Darimont B,Hager JH

更新日期：2013-09-01 00:00:00

abstract：:CD30-directed CAR T cells were safe and produced a 62% overall response rate in Hodgkin lymphoma. ...

journal_title：Cancer discovery

authors：

更新日期：2020-09-01 00:00:00

abstract：:Global remodeling of the chromatin landscape occurs during senescence, although its functional consequence is still unclear. In this issue, Tasdemir and colleagues show that the epigenetic regulator BRD4 is required for expression of the proinflammatory senescence-associated secretory phenotype and immune clearance of...

journal_title：Cancer discovery

authors： Vizioli MG,Adams PD

更新日期：2016-06-01 00:00:00

abstract：:HDAC inhibitors synergize with PI3K inhibitors to reduce MYC-driven medulloblastoma (MB) growth. ...

journal_title：Cancer discovery

authors：

更新日期：2016-05-01 00:00:00

abstract：:Spliceosome inhibitors induced mRNA missplicing, retaining introns that formed double-stranded RNA. ...

journal_title：Cancer discovery

authors：

更新日期：2021-01-22 00:00:00

abstract：:An international team of researchers has uncovered multiple new germline mutations that may influence the development of sarcomas. Notably, they found that variants in several DNA damage sensing and repair genes contribute greatly to sarcoma risk, including BRCA2, ATM, ATR, and ERCC2. ...

journal_title：Cancer discovery

authors：

更新日期：2016-10-01 00:00:00

abstract：:The NCI and Department of Veterans Affairs (VA) are collaborating on the NCI and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, which will launch at 12 VA facilities across the country. The program aims to increase participation of veterans with cancer in NCI-sponsored clinical trials. ...

journal_title：Cancer discovery

authors：

更新日期：2018-08-01 00:00:00