A Set of Transcriptomic Changes Is Associated with Anti-PD-1 Resistance.

abstract：:Identifying the cancer cells-of-origin is of great interest, as it holds the potential to elucidate biologic mechanisms inherent in the normal cell state that have been co-opted to drive the oncogenic cell state. An emerging concept, proposed here, states that cancer stem cells, key players in cancer initiation and me...

journal_title：Cancer discovery

authors： Chaffer CL,Weinberg RA

更新日期：2015-01-01 00:00:00

abstract：:E3 ubiquitin ligases are of interest as drug targets for their ability to regulate protein stability and function. The oncogene Mdm2 is an attractive E3 ligase to target, as it is the key negative regulator of the tumor suppressor p53, which controls the transcription of genes involved in cell fate. Overexpression of ...

journal_title：Cancer discovery

authors： Herman AG,Hayano M,Poyurovsky MV,Shimada K,Skouta R,Prives C,Stockwell BR

更新日期：2011-09-01 00:00:00

abstract：:The pks+E. coli metabolite colibactin caused a unique mutational signature in intestinal organoids. ...

journal_title：Cancer discovery

authors：

更新日期：2020-05-01 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：UNLABELLED:Knowledge of "actionable" somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic ...

journal_title：Cancer discovery

authors： Wagle N,Berger MF,Davis MJ,Blumenstiel B,Defelice M,Pochanard P,Ducar M,Van Hummelen P,Macconaill LE,Hahn WC,Meyerson M,Gabriel SB,Garraway LA

更新日期：2012-01-01 00:00:00

abstract：:A recent clinical trial shows that sorafenib is effective against desmoid tumors. The study found that 33% of tumors shrank in patients who received the drug. The estimated 1-year progression-free survival for the sorafenib-treated patients was 89%, and the 2-year rate was 81%. ...

journal_title：Cancer discovery

authors：

更新日期：2019-03-01 00:00:00

abstract：:The EGFR inhibitor osimertinib may be an effective therapy for patients with untreated non-small cell lung cancer who have brain metastases. In a recent study, the drug extended median progression-free survival and increased objective response rates compared with the first-generation EGFR inhibitors gefitinib and erlo...

journal_title：Cancer discovery

authors：

更新日期：2018-11-01 00:00:00

abstract：:T cell-based therapies have induced cancer remissions, though most tumors ultimately progress, reflecting inherent or acquired resistance including antigen escape. Better understanding of how T cells eliminate tumors will help decipher resistance mechanisms. We used a CRISPR/Cas9 screen and identified a necessary role...

journal_title：Cancer discovery

authors： Upadhyay R,Boiarsky JA,Pantsulaia G,Svensson-Arvelund J,Lin MJ,Wroblewska A,Bhalla S,Scholler N,Bot A,Rossi JM,Sadek N,Parekh S,Laganà A,Baccarini A,Merad M,Brown BD,Brody JD

更新日期：2020-12-17 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：:Mutating a conserved motif in the activation loop of MEC1 (ATR) revealed the activation mechanism. ...

journal_title：Cancer discovery

authors：

更新日期：2020-11-20 00:00:00

abstract：:Epigenetic regulators, when genomically altered, may become driver oncogenes that mediate otherwise unexplained pro-oncogenic changes lacking a clear genetic stimulus, such as activation of the WNT/β-catenin pathway in melanoma. This study identifies previously unrecognized recurrent activating mutations in the G9a hi...

journal_title：Cancer discovery

authors： Kato S,Weng QY,Insco ML,Chen KY,Muralidhar S,Pozniak J,Diaz JMS,Drier Y,Nguyen N,Lo JA,van Rooijen E,Kemeny LV,Zhan Y,Feng Y,Silkworth W,Powell CT,Liau BB,Xiong Y,Jin J,Newton-Bishop J,Zon LI,Bernstein BE,Fish

更新日期：2020-07-01 00:00:00

abstract：:In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB...

journal_title：Cancer discovery

authors： Tsay JJ,Wu BG,Sulaiman I,Gershner K,Schluger R,Li Y,Yie TA,Meyn P,Olsen E,Perez L,Franca B,Carpenito J,Iizumi T,El-Ashmawy M,Badri M,Morton JT,Shen N,He L,Michaud G,Rafeq S,Bessich JL,Smith RL,Sauthoff H,Fel

更新日期：2020-11-11 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：UNLABELLED:B-cell lymphomas frequently contain genomic rearrangements that lead to oncogene activation by heterologous distal regulatory elements. We used a novel approach called "pinpointing enhancer-associated rearrangements by chromatin immunoprecipitation," or PEAR-ChIP, to simultaneously map enhancer activity and ...

journal_title：Cancer discovery

authors： Ryan RJ,Drier Y,Whitton H,Cotton MJ,Kaur J,Issner R,Gillespie S,Epstein CB,Nardi V,Sohani AR,Hochberg EP,Bernstein BE

更新日期：2015-10-01 00:00:00

abstract：UNLABELLED:Next-generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple-negative breast cancers (TNBC; 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associ...

journal_title：Cancer discovery

authors： Stoeck A,Lejnine S,Truong A,Pan L,Wang H,Zang C,Yuan J,Ware C,MacLean J,Garrett-Engele PW,Kluk M,Laskey J,Haines BB,Moskaluk C,Zawel L,Fawell S,Gilliland G,Zhang T,Kremer BE,Knoechel B,Bernstein BE,Pear WS,Liu

更新日期：2014-10-01 00:00:00

abstract：:Inosine produced by the gut microbe Bifidobacterium pseudolongum enhanced anti-CTLA4's efficacy. ...

journal_title：Cancer discovery

authors：

更新日期：2020-10-01 00:00:00

abstract：:Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, g...

journal_title：Cancer discovery

authors： Clarke M,Mackay A,Ismer B,Pickles JC,Tatevossian RG,Newman S,Bale TA,Stoler I,Izquierdo E,Temelso S,Carvalho DM,Molinari V,Burford A,Howell L,Virasami A,Fairchild AR,Avery A,Chalker J,Kristiansen M,Haupfear K,Dalt

更新日期：2020-07-01 00:00:00

abstract：UNLABELLED:Genetic approaches have shown that the p110β isoform of class Ia phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null tumors. Thus, it is desirable to develop p110β-specific inhibitors for cancer therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a collectio...

journal_title：Cancer discovery

authors： Ni J,Liu Q,Xie S,Carlson C,Von T,Vogel K,Riddle S,Benes C,Eck M,Roberts T,Gray N,Zhao J

更新日期：2012-05-01 00:00:00

abstract：:Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4-CD8-NK1.1- innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and human...

journal_title：Cancer discovery

authors： Hundeyin M,Kurz E,Mishra A,Rossi JAK,Liudahl SM,Leis KR,Mehrotra H,Kim M,Torres LE,Ogunsakin A,Link J,Sears RC,Sivagnanam S,Goecks J,Islam KMS,Dolgalev I,Savadkar S,Wang W,Aykut B,Leinwand J,Diskin B,Adam S,Is

更新日期：2019-09-01 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：:It is possible to decipher the clonal architecture of a tumor and the sequence in which cancer clones acquire genomic alterations through multiregion sequencing (M-seq). Serial evaluation of tumor specimens through M-seq can provide valuable information on the molecular basis of resistance to therapy. ...

journal_title：Cancer discovery

authors： Devarakonda S,Govindan R

更新日期：2015-08-01 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：:An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of its kind approved for cancer and has the potential to transform standard of...

journal_title：Cancer discovery

authors：

更新日期：2017-09-01 00:00:00

abstract：:Researchers have developed an antibody-drug conjugate with the potential to treat neuroblastoma. The agent targets ALK, which is found on neuroblastoma cells but not healthy cells, delivering a drug that causes DNA cross-links. Researchers have found that the antibody-drug conjugate kills ALK-expressing cells in vitro...

journal_title：Cancer discovery

authors：

更新日期：2019-06-01 00:00:00

abstract：:Whether metastases were seeded mono- or polyclonally depended on cancer site and treatment. ...

journal_title：Cancer discovery

authors：

更新日期：2020-07-01 00:00:00

abstract：:Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment. Here, we show that Notch in tumor cells regulates the expression of two powerful proinflammatory cytokines, IL1β and CCL2, and the recruitment of tumo...

journal_title：Cancer discovery

authors： Shen Q,Cohen B,Zheng W,Rahbar R,Martin B,Murakami K,Lamorte S,Thompson P,Berman H,Zúñiga-Pflücker JC,Ohashi PS,Reedijk M

更新日期：2017-11-01 00:00:00

abstract：:A report from the Presidential Commission for the Study of Bioethical Issues offers several recommendations to help protect the privacy of patients who have whole-genome sequencing. ...

journal_title：Cancer discovery

authors：

更新日期：2012-12-01 00:00:00

abstract：: In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the centra...