NK Cells Respond to Checkpoint Blockade.

abstract：UNLABELLED:ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. ...

journal_title：Cancer discovery

authors： Shen J,Peng Y,Wei L,Zhang W,Yang L,Lan L,Kapoor P,Ju Z,Mo Q,Shih IeM,Uray IP,Wu X,Brown PH,Shen X,Mills GB,Peng G

更新日期：2015-07-01 00:00:00

abstract：UNLABELLED:Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as "undruggable." We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with...

journal_title：Cancer discovery

authors： Sen M,Thomas SM,Kim S,Yeh JI,Ferris RL,Johnson JT,Duvvuri U,Lee J,Sahu N,Joyce S,Freilino ML,Shi H,Li C,Ly D,Rapireddy S,Etter JP,Li PK,Wang L,Chiosea S,Seethala RR,Gooding WE,Chen X,Kaminski N,Pandit K,Jo

更新日期：2012-08-01 00:00:00

abstract：:To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutro...

journal_title：Cancer discovery

authors： Gil Del Alcazar CR,Huh SJ,Ekram MB,Trinh A,Liu LL,Beca F,Zi X,Kwak M,Bergholtz H,Su Y,Ding L,Russnes HG,Richardson AL,Babski K,Min Hui Kim E,McDonnell CH 3rd,Wagner J,Rowberry R,Freeman GJ,Dillon D,Sorlie T,Cous

更新日期：2017-10-01 00:00:00

abstract：UNLABELLED:Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell cul...

journal_title：Cancer discovery

authors： Bose R,Kavuri SM,Searleman AC,Shen W,Shen D,Koboldt DC,Monsey J,Goel N,Aronson AB,Li S,Ma CX,Ding L,Mardis ER,Ellis MJ

更新日期：2013-02-01 00:00:00

abstract：:Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer. Improved progression-free survival was seen regardless of the presence or absence of germline BRCA mutations, or o...

journal_title：Cancer discovery

authors：

更新日期：2016-12-01 00:00:00

abstract：:The Ivy Glioblastoma Atlas provides detailed information about genes expressed in different anatomic regions of human brain tumors. Researchers are already drawing upon the resource to identify novel therapeutic targets for this deadly cancer. ...

journal_title：Cancer discovery

authors：

更新日期：2018-07-01 00:00:00

abstract：:Long ignored, the importance of circadian rhythms-the focus of this year's Nobel Prize in Physiology or Medicine-is beginning to gain attention from researchers interested in cancer prevention, drug discovery, and therapeutic optimization. ...

journal_title：Cancer discovery

authors：

更新日期：2017-12-01 00:00:00

abstract：:Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel-Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal p...

journal_title：Cancer discovery

authors： Yao X,Tan J,Lim KJ,Koh J,Ooi WF,Li Z,Huang D,Xing M,Chan YS,Qu JZ,Tay ST,Wijaya G,Lam YN,Hong JH,Lee-Lim AP,Guan P,Ng MSW,He CZ,Lin JS,Nandi T,Qamra A,Xu C,Myint SS,Davies JOJ,Goh JY,Loh G,Tan BC,Roz

更新日期：2017-11-01 00:00:00

abstract：:Margetuximab outperformed trastuzumab in a phase III, head-to-head trial of the two anti-HER2 agents among patients with HER2-positive metastatic breast cancer. The new antibody drug was engineered for enhanced immune activity against HER2-expressing tumor cells. ...

journal_title：Cancer discovery

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更新日期：2019-08-01 00:00:00

abstract：:BRAF inhibitors stabilize a closed, rigid RAF kinase conformation that facilitates dimerization. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：UNLABELLED:Pancreatic ductal adenocarcinoma is refractory to available therapies. We have previously shown that these tumors have elevated autophagy and that inhibition of autophagy leads to decreased tumor growth. Using an autochthonous model of pancreatic cancer driven by oncogenic Kras and the stochastic LOH of Trp5...

journal_title：Cancer discovery

authors： Yang A,Rajeshkumar NV,Wang X,Yabuuchi S,Alexander BM,Chu GC,Von Hoff DD,Maitra A,Kimmelman AC

更新日期：2014-08-01 00:00:00

abstract：UNLABELLED:Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood. Through an integrated analysis of cell lines, in vivo models, and clinical samples, we demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), ...

journal_title：Cancer discovery

authors： Tanaka K,Babic I,Nathanson D,Akhavan D,Guo D,Gini B,Dang J,Zhu S,Yang H,De Jesus J,Amzajerdi AN,Zhang Y,Dibble CC,Dan H,Rinkenbaugh A,Yong WH,Vinters HV,Gera JF,Cavenee WK,Cloughesy TF,Manning BD,Baldwin AS,Mi

更新日期：2011-11-01 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：UNLABELLED:CD96 has recently been shown as a negative regulator of mouse natural killer (NK)-cell activity, with Cd96(-/-)mice displaying hyperresponsive NK cells upon immune challenge. In this study, we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in three different...

journal_title：Cancer discovery

authors： Blake SJ,Stannard K,Liu J,Allen S,Yong MC,Mittal D,Aguilera AR,Miles JJ,Lutzky VP,de Andrade LF,Martinet L,Colonna M,Takeda K,Kühnel F,Gurlevik E,Bernhardt G,Teng MW,Smyth MJ

更新日期：2016-04-01 00:00:00

abstract：UNLABELLED:Indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have entered clinical trials for cancer treatment based on preclinical studies, indicating that they can defeat immune escape and broadly enhance other therapeutic modalities. However, clear genetic evidence of the impact of IDO on tumorigenesis in physiolo...

journal_title：Cancer discovery

authors： Smith C,Chang MY,Parker KH,Beury DW,DuHadaway JB,Flick HE,Boulden J,Sutanto-Ward E,Soler AP,Laury-Kleintop LD,Mandik-Nayak L,Metz R,Ostrand-Rosenberg S,Prendergast GC,Muller AJ

更新日期：2012-08-01 00:00:00

abstract：:Activating mutations in the EGF receptor (EGFR) are associated with clinical responsiveness to EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib. However, resistance eventually arises, often due to a second EGFR mutation, most commonly T790M. Through a genome-wide siRNA screen in a human lung canc...

journal_title：Cancer discovery

authors： de Bruin EC,Cowell C,Warne PH,Jiang M,Saunders RE,Melnick MA,Gettinger S,Walther Z,Wurtz A,Heynen GJ,Heideman DA,Gómez-Román J,García-Castaño A,Gong Y,Ladanyi M,Varmus H,Bernards R,Smit EF,Politi K,Downward J

更新日期：2014-05-01 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：:In the plasmaMATCH trial, researchers performed circulating tumor DNA testing on patients with advanced breast cancer and matched those with ESR1, HER2, or AKT1 alterations to targeted therapies. Patients with HER2 and AKT1 mutations experienced response rates greater than 22% with durable benefit. ...

journal_title：Cancer discovery

authors：

更新日期：2020-05-01 00:00:00

abstract：:LXR activation reduces immunosuppressive MDSCs to activate antitumor cytotoxic T cells. ...

journal_title：Cancer discovery

authors：

更新日期：2018-03-01 00:00:00

abstract：:Accelerated review and greater understanding of tumor biology speed targeted treatments to patients. ...

journal_title：Cancer discovery

authors： Rose S

更新日期：2011-10-01 00:00:00

abstract：:Tumors mutated in IDH1 tend to have lower levels of the essential substrate NAD+. In this issue of Cancer Discovery, Nagashima and colleagues exploit this metabolic sensitivity by devising a combinatorial therapy that both further reduces the pools as well as sequesters the remaining substrate in PAR chains, sensitizi...

journal_title：Cancer discovery

authors： Pirozzi CJ,Yan H

更新日期：2020-11-01 00:00:00

abstract：:Hypoxia-inducible factors (HIF) have long been linked to malignant tumor phenotypes in various cancer types, and several downstream mediators of HIF action are deregulated in metastatic carcinomas. A new study links hypoxia-induced collagen remodeling to sarcoma progression, providing evidence for unifying mechanisms ...

journal_title：Cancer discovery

authors： Vanharanta S,Massagué J

更新日期：2013-10-01 00:00:00

abstract：:A recent study suggests that complex genomic rearrangements in triple-negative breast cancer cells occur through a "Big Bang" model-early, short bursts of copy number aberrations, rather than progressive accumulation over time. Afterward, these aberrations are stably maintained in a handful of clones that expand to fo...

journal_title：Cancer discovery

authors：

更新日期：2016-10-01 00:00:00

abstract：:Metabolic reprogramming enables cancer cell growth, proliferation, and survival. This reprogramming is driven by the combined actions of oncogenic alterations in cancer cells and host cell factors acting on cancer cells in the tumor microenvironment. Cancer cell intrinsic mechanisms activate signal transduction compon...

journal_title：Cancer discovery

authors： Dey P,Kimmelman AC,DePinho RA

更新日期：2021-01-27 00:00:00

abstract：:The combination of the antibody-drug conjugate ado-trastuzumab emtansine, or T-DM1, plus pertuzumab given prior to surgery outperformed standard therapy in women with HER2-positive breast cancer enrolled in the I-SPY 2 trial. The results, reported at the American Association for Cancer Research Annual Meeting 2016, su...

journal_title：Cancer discovery

authors：

更新日期：2016-06-01 00:00:00

abstract：:In this issue of Cancer Discovery, Auciello and colleagues find that in the pancreatic cancer microenvironment activated fibroblasts secrete specific lipids that provide a source of biomass production and signaling molecules for cancer cells, fueling their proliferation and migration. Targeting of this stromal-tumor m...

journal_title：Cancer discovery

authors： Biffi G,Tuveson DA

更新日期：2019-05-01 00:00:00

abstract：:An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use ...

journal_title：Cancer discovery

authors： MacConaill LE,Van Hummelen P,Meyerson M,Hahn WC

更新日期：2011-09-01 00:00:00

abstract：:Immune checkpoint inhibitors (ICI) targeting CTLA-4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events (irAEs), including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which mono-allelic loss of Ctla4 in the context of co...

journal_title：Cancer discovery

authors： Wei SC,Meijers WC,Axelrod ML,Anang NAS,Screever EM,Wescott EC,Johnson DB,Whitley E,Lehmann L,Courand PY,Mancuso JJ,Himmel LE,Lebrun-Vignes B,Wleklinski MJ,Knollmann BC,Srinivasan J,Li Y,Atolagbe OT,Rao X,Zhao Y,Wa

更新日期：2020-11-30 00:00:00

abstract：:Treating human breast cancer xenografts in mice with bevacizumab or sunitinib has increased the population of cancer stem cells found in the tumors. ...

journal_title：Cancer discovery

authors：

更新日期：2012-03-01 00:00:00

abstract：:The FDA granted accelerated approval to selinexor plus low-dose dexamethasone for triple-class refractory multiple myeloma, despite an advisory panel's concerns about the drug's toxicity and the lack of randomized clinical data. ...

journal_title：Cancer discovery

authors：

更新日期：2019-09-01 00:00:00