Engineering Multidimensional Evolutionary Forces to Combat Cancer.

abstract：UNLABELLED:Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase fami...

journal_title：Cancer discovery

authors： Sanda T,Tyner JW,Gutierrez A,Ngo VN,Glover J,Chang BH,Yost A,Ma W,Fleischman AG,Zhou W,Yang Y,Kleppe M,Ahn Y,Tatarek J,Kelliher MA,Neuberg DS,Levine RL,Moriggl R,Müller M,Gray NS,Jamieson CH,Weng AP,Staudt LM

更新日期：2013-05-01 00:00:00

abstract：:Recent findings from a phase II trial suggest that combining the antiandrogen abiraterone and the PARP inhibitor olaparib significantly improves progression-free survival among patients with metastatic castration-resistant prostate cancer, regardless of their homologous recombination repair-mutation status. ...

journal_title：Cancer discovery

authors：

更新日期：2018-08-01 00:00:00

abstract：:The new iRECIST guideline-developed in consultation with academics, drug companies, and regulatory authorities-provides a standardized approach to assessing whether patients' disease improves, stays the same, or worsens in trials of immunotherapeutics, agents that can trigger different response patterns from other kin...

journal_title：Cancer discovery

authors：

更新日期：2017-05-01 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：:Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression and are involved in cancer pathogenesis. Over the last years, several BET inhibitors have been developed and clinically tested. Results from the first clinical trials show limited single-agent activity in a small s...

journal_title：Cancer discovery

authors： Stathis A,Bertoni F

更新日期：2018-01-01 00:00:00

abstract：:Drug-induced apoptosis occurs after cells reach a p53 threshold level, which increases over time. ...

journal_title：Cancer discovery

authors：

更新日期：2016-06-01 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

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更新日期：2013-07-01 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：:Researchers have presented a new model that uses six readily available clinical factors to predict whether a patient with advanced bladder cancer who has already received platinum chemotherapy will respond to treatment with the PD-L1 inhibitor atezolizumab. The results may help patients and their doctors decide how to...

journal_title：Cancer discovery

authors：

更新日期：2018-04-01 00:00:00

abstract：:Investigators have discovered that a certain type of immune cell in tumors, known as tissue-resident memory cells, are associated with a strong immune response and improved prognosis in lung cancer. The findings may aid in selecting appropriate immunotherapies and developing more effective vaccines for a wide range of...

journal_title：Cancer discovery

authors：

更新日期：2017-09-01 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：: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：SUMMARY:In this issue of Cancer Discovery, Romero and colleagues identify somatic mutations and deletions of MAX, and also define what seem to be mutually exclusive alterations in MYC family members and other MYC-associated factors in small cell lung cancer. Taken together, these data highlight the importance of MYC si...

journal_title：Cancer discovery

authors： Rudin CM,Poirier JT

更新日期：2014-03-01 00:00:00

abstract：:The IPRES signature is related to anti-PD-1 response, and high mutational load predicts survival. ...

journal_title：Cancer discovery

authors：

更新日期：2016-05-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abunda...

journal_title：Cancer discovery

authors： Carrer A,Trefely S,Zhao S,Campbell SL,Norgard RJ,Schultz KC,Sidoli S,Parris JLD,Affronti HC,Sivanand S,Egolf S,Sela Y,Trizzino M,Gardini A,Garcia BA,Snyder NW,Stanger BZ,Wellen KE

更新日期：2019-03-01 00:00:00

abstract：:Researchers have used mass spectrometry to conduct proteomic analyses of 77 genomically characterized breast tumors. Through this approach, they've uncovered functional consequences of somatic mutations. For instance, EGFR overexpression in basal-like breast cancer is potentially driven by the loss of two genes, SKP1 ...

journal_title：Cancer discovery

authors：

更新日期：2016-08-01 00:00:00

abstract：:A report from the National Academies of Sciences, Engineering, and Medicine lays out 12 recommendations to help scientists decide whether to return research results to study participants and, if they do, how to improve the sharing of information. The most important change the report recommends is harmonizing contradic...

journal_title：Cancer discovery

authors：

更新日期：2018-09-01 00:00:00

abstract：:In a phase I trial, the DARPin MG0250 had an expected safety profile and early signs of efficacy. ...

journal_title：Cancer discovery

authors：

更新日期：2021-01-08 00:00:00

abstract：:Gilead Sciences will buy Kite Pharma-and its autologous CAR T-cell technology-for $11.9 billion. The acquisition will help Gilead build its oncology portfolio and boost its revenues. ...

journal_title：Cancer discovery

authors：

更新日期：2017-10-01 00:00:00

abstract：:In the ECHO-202/KEYNOTE-037 and ECHO-204 trials reported at the 2017 Annual Meeting of the American Society of Clinical Oncology, patients with squamous cell carcinoma of the head and neck responded well to the combinations of epacadostat plus pembrolizumab and epacadostat plus nivolumab. An IDO1 inhibitor, epacadosta...

journal_title：Cancer discovery

authors：

更新日期：2017-09-01 00:00:00

abstract：:Domchek and colleagues provide a case report of a 28-year-old woman with congenital abnormalities, inherited ovarian cancer, and carboplatin hypersensitivity. Interestingly, the woman had validated germline mutations in both BRCA1 alleles. These findings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and h...

journal_title：Cancer discovery

authors： D'Andrea AD

更新日期：2013-04-01 00:00:00

abstract：:In the largest clinical trial to date of immune checkpoint inhibitors for mesothelioma, patients treated with nivolumab-either alone or in combination with ipilimumab-posted impressive response rates and survival outcomes, according to data presented at the 2017 American Society of Clinical Oncology Annual Meeting. Ho...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 00:00:00

abstract：:A new compound with anti-leukemia activity perturbs gene transcription by modulating super-enhancer activity. ...

journal_title：Cancer discovery

authors：

更新日期：2015-12-01 00:00:00

abstract：:Three genetic markers performed far better than histologic criteria to classify diffuse low-grade gliomas, laying the foundation for molecular diagnosis of this heterogeneous group of brain tumors. ...

journal_title：Cancer discovery

authors：

更新日期：2015-08-01 00:00:00

abstract：:The FDA granted accelerated approval to palbociclib for the treatment of estrogen receptor-positive, HER2-negative metastatic breast cancer in postmenopausal women who have not yet received endocrine-based therapy. Palbociclib is the first cell cycle-targeting CDK 4/6 inhibitor to reach the market. ...

journal_title：Cancer discovery

authors：

更新日期：2015-04-01 00:00:00

abstract：:Ceritinib and other second-generation inhibitors have demonstrated promising anticancer activity in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Specifically, they can overcome resistance due to certain gatekeeper mutations acquired following crizotinib exposure. These agents now provi...

journal_title：Cancer discovery

authors： Ramalingam SS,Khuri FR

更新日期：2014-06-01 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：: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：: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：: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