Cancer "Clock" Opens New Therapeutic Avenues.

abstract：:With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we e...

journal_title：Cancer discovery

authors： McCoach CE,Bivona TG

更新日期：2019-05-01 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

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更新日期：2021-01-08 00:00:00

abstract：:The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ...

journal_title：Cancer discovery

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更新日期：2017-06-01 00:00:00

abstract：:In a phase Ib trial, a combination of the experimental immunotherapy AM0010, a PEGylated form of the recombinant human cytokine IL10, and the anti-PD-1 checkpoint inhibitor pembrolizumab was well tolerated and effective at controlling tumors in some patients with advanced renal cell carcinoma, non-small cell lung canc...

journal_title：Cancer discovery

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更新日期：2016-12-01 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：:Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to therapies and histologically contains a paucity of neoplastic cells embedded within a dense desmoplastic stroma. Within the stroma, cancer-associated fibroblasts (CAF) secrete tropic factors and extracellular matrix components, and have been implicated in...

journal_title：Cancer discovery

authors： Biffi G,Oni TE,Spielman B,Hao Y,Elyada E,Park Y,Preall J,Tuveson DA

更新日期：2019-02-01 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：UNLABELLED:In human chronic lymphocytic leukemia (CLL) pathogenesis, B-cell antigen receptor signaling seems important for leukemia B-cell ontogeny, whereas the microenvironment influences B-cell activation, tumor cell lodging, and provision of antigenic stimuli. Using the murine Eμ-Tcl1 CLL model, we demonstrate that ...

journal_title：Cancer discovery

authors： Heinig K,Gätjen M,Grau M,Stache V,Anagnostopoulos I,Gerlach K,Niesner RA,Cseresnyes Z,Hauser AE,Lenz P,Hehlgans T,Brink R,Westermann J,Dörken B,Lipp M,Lenz G,Rehm A,Höpken UE

更新日期：2014-12-01 00:00:00

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：:Critically short telomeres activate cellular senescence or apoptosis, as mediated by the tumor suppressor p53, but in the absence of this checkpoint response, telomere dysfunction engenders chromosomal aberrations and cancer. Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identi...

journal_title：Cancer discovery

authors： Zhang Y,Shin SJ,Liu D,Ivanova E,Foerster F,Ying H,Zheng H,Xiao Y,Chen Z,Protopopov A,Depinho RA,Paik JH

更新日期：2013-07-01 00:00:00

abstract：:Ubiquitin-specific protease 2a, a deubiquitinating enzyme, elevates MYC levels in prostate cancer cells via its stabilization of MDM2, undermining p53 regulation of microRNAs that target MYC mRNA. ...

journal_title：Cancer discovery

authors： Nelson WG,De Marzo AM,Yegnasubramanian S

更新日期：2012-03-01 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：:An intact gut microbiome was needed to protect genetically vulnerable mice from developing leukemia. ...

journal_title：Cancer discovery

authors：

更新日期：2020-11-01 00:00:00

abstract：:According to a prospective genomic analysis, Lynch syndrome may be linked with a broader spectrum of tumor types beyond colorectal and endometrial cancers. The results suggest that patients with MSI-high tumors, regardless of type, should undergo germline testing for this condition. ...

journal_title：Cancer discovery

authors：

更新日期：2018-08-01 00:00:00

abstract：:Celgene acquired Juno Therapeutics for $9 billion and is spending up to $7 billion on Impact Biomedicines in an effort to diversify its hematology portfolio with chimeric antigen receptor T-cell therapies and a JAK2 inhibitor before its best seller, lenalidomide, faces competition from generics. ...

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：: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：:Kidney cancer is not a single disease but represents several distinct types of cancer that have defining histologies and genetic alterations and that follow different clinical courses and have different responses to therapy. Mutation of genes associated with kidney cancer, such as VHL, FLCN, TFE3, FH, or SDHB, dysregu...

journal_title：Cancer discovery

authors： Linehan WM,Schmidt LS,Crooks DR,Wei D,Srinivasan R,Lang M,Ricketts CJ

更新日期：2019-08-01 00:00:00

abstract：UNLABELLED:Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which control access to an allosteric pocket adjacent to the ATP-binding site, has ...

journal_title：Cancer discovery

authors： Smith CC,Zhang C,Lin KC,Lasater EA,Zhang Y,Massi E,Damon LE,Pendleton M,Bashir A,Sebra R,Perl A,Kasarskis A,Shellooe R,Tsang G,Carias H,Powell B,Burton EA,Matusow B,Zhang J,Spevak W,Ibrahim PN,Le MH,Hsu HH,H

更新日期：2015-06-01 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：: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 U.S. Preventive Services Task Force released new guidelines recommending BRCA mutation testing be limited to high-risk women who have received genetic counseling. ...

journal_title：Cancer discovery

authors：

更新日期：2014-02-01 00:00:00

abstract：:Ionizing irradiation and PD-L1 blockade synergistically enhance antitumor immunity. ...

journal_title：Cancer discovery

authors：

更新日期：2014-03-01 00:00:00

abstract：:53BP1 requires RIF1 to block 5' end resection required for homologous recombination. ...

journal_title：Cancer discovery

authors：

更新日期：2013-03-01 00:00:00

abstract：:A recent study integrating proteomic and genomic analyses uncovered unexpected similarities in some types of pediatric brain tumors, such as certain craniopharyngiomas and low-grade gliomas, suggesting potential treatments and more refined prognoses. ...

journal_title：Cancer discovery

authors：

更新日期：2021-01-07 00:00:00

abstract：:Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we rep...

journal_title：Cancer discovery

authors： Pei S,Pollyea DA,Gustafson A,Stevens BM,Minhajuddin M,Fu R,Riemondy KA,Gillen AE,Sheridan RM,Kim J,Costello JC,Amaya ML,Inguva A,Winters A,Ye H,Krug A,Jones CL,Adane B,Khan N,Ponder J,Schowinsky J,Abbott D,Ham

更新日期：2020-04-01 00:00:00

abstract：:Findings from a phase I/IIa study indicate that combining the investigational indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and boosts response rates among patients with bladder and cervical cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2018-01-01 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：: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：: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