abstract：:Pemigatinib was effective in patients with cholangiocarcinomas with FGFR2 fusions or rearrangements. ...

journal_title：Cancer discovery

authors：

更新日期：2020-05-01 00:00:00

abstract：:HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant so...

journal_title：Cancer discovery

authors： Tsurutani J,Iwata H,Krop I,Jänne PA,Doi T,Takahashi S,Park H,Redfern C,Tamura K,Wise-Draper TM,Saito K,Sugihara M,Singh J,Jikoh T,Gallant G,Li BT

更新日期：2020-05-01 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：:The structure of CD20 with the antibody drug rituximab showed the binding mode and 2:2 stoichiometry. ...

journal_title：Cancer discovery

authors：

更新日期：2020-04-01 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：:AKT inhibitors have promising activity in AKT1E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinica...

journal_title：Cancer discovery

authors： Smyth LM,Zhou Q,Nguyen B,Yu C,Lepisto EM,Arnedos M,Hasset MJ,Lenoue-Newton ML,Blauvelt N,Dogan S,Micheel CM,Wathoo C,Horlings H,Hudecek J,Gross BE,Kundra R,Sweeney SM,Gao J,Schultz N,Zarski A,Gardos SM,Lee J,S

更新日期：2020-04-01 00:00:00

abstract：:The structure of the chromatin-remodeling BAF complex provides molecular-scale mechanistic insight. ...

journal_title：Cancer discovery

authors：

更新日期：2020-03-01 00:00:00

abstract：:Granule neuron precursors transdifferentiate into astrocytes in the tumor microenvironment. ...

journal_title：Cancer discovery

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更新日期：2020-03-01 00:00:00

abstract：:Although BRAF-MEK inhibition can enhance the immune recognition of melanoma cells, the mechanisms that underlie this remain poorly defined. In this issue of Cancer Discovery, Erkes and colleagues present new data showing that BRAF-MEK inhibition activates pyroptosis in melanoma cells through gasdermin E cleavage, lead...

journal_title：Cancer discovery

authors： Smalley KSM

更新日期：2020-02-01 00:00:00

abstract：:Hallin and colleagues demonstrate the preclinical activity of the KRASG12C-specific inhibitor MRTX849 in a series of in vitro and in vivo studies with supporting pilot clinical efficacy. Variable responsiveness despite effective KRASG12C inhibition highlights both the promise and potential need for combinatorial strat...

journal_title：Cancer discovery

authors： Klempner SJ,Hata AN

更新日期：2020-01-01 00:00:00

abstract：:Recent results suggest that tucatinib, when combined with trastuzumab and capecitabine, is effective in patients with locally advanced inoperable or metastatic HER2-positive breast cancer who have received prior therapies: In a phase II trial, the drug extended overall survival and progression-free survival compared w...

journal_title：Cancer discovery

authors：

更新日期：2020-01-01 00:00:00

abstract：:Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide with no clinically confirmed oncogenic driver. Although preclinical studies implicate the FGF19 receptor FGFR4 in hepatocarcinogenesis, the dependence of human cancer on FGFR4 has not been demonstrated. Fisogatinib (BLU-554) is a potent an...

journal_title：Cancer discovery

authors： Hatlen MA,Schmidt-Kittler O,Sherwin CA,Rozsahegyi E,Rubin N,Sheets MP,Kim JL,Miduturu C,Bifulco N,Brooijmans N,Shi H,Guzi T,Boral A,Lengauer C,Dorsch M,Kim RD,Kang YK,Wolf BB,Hoeflich KP

更新日期：2019-12-01 00:00:00

abstract：:The Genomics of Drug Sensitivity in Cancer project recently added 4 years of additional data to a large-scale database designed to identify predictive biomarkers for cancer therapies. Freely available online, these data are driving research on the relationship between genomic features and drug responses to better tail...

journal_title：Cancer discovery

authors：

更新日期：2019-11-01 00:00:00

abstract：:STAT3 palmitoylation increases dimerization, nuclear localization, and activation of target genes. ...

journal_title：Cancer discovery

authors：

更新日期：2019-09-06 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：: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

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

authors：

更新日期：2019-08-01 00:00:00

abstract：:Amgen's novel small-molecule inhibitor AMG 510 has become the first drug to successfully target a KRAS mutation in patients, according to findings presented at the 2019 American Society of Clinical Oncology Annual Meeting. In a phase I trial, AMG 510 elicited partial responses in half of evaluable patients with KRASG1...

journal_title：Cancer discovery

authors：

更新日期：2019-08-01 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：:According to results from ENZAMET, a global phase III trial, adding enzalutamide to standard treatment for men with metastatic hormone-sensitive prostate cancer is superior in prolonging survival compared with older nonsteroidal antiandrogen drugs. ...

journal_title：Cancer discovery

authors：

更新日期：2019-08-01 00:00:00

abstract：:A recent study investigated the mechanisms underlying the interaction between olaparib and cediranib in non-BRCA-mutant ovarian cancer. Cediranib may confer sensitivity to olaparib by increasing tumor hypoxia and inhibiting platelet-derived growth factor receptor, which reduces BRCA1/2 and RAD51 expression, thus decre...

journal_title：Cancer discovery

authors：

更新日期：2019-08-01 00:00:00

abstract：:To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen to identify gene knockouts resulting in drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results in venetoclax resistance in AML cell lines...

journal_title：Cancer discovery

authors： Nechiporuk T,Kurtz SE,Nikolova O,Liu T,Jones CL,D'Alessandro A,Culp-Hill R,d'Almeida A,Joshi SK,Rosenberg M,Tognon CE,Danilov AV,Druker BJ,Chang BH,McWeeney SK,Tyner JW

更新日期：2019-07-01 00:00:00

abstract：:Tagraxofusp-erzs is an effective therapy for blastic plasmacytoid dendritic-cell neoplasm, according to recently published results from a multistage trial that led to the drug's 2018 approval. In the trial, the drug elicited high overall response rates, and many patients went on to receive a stem-cell transplant. Howe...

journal_title：Cancer discovery

authors：

更新日期：2019-07-01 00:00:00

abstract：:In this issue of Cancer Discovery, Poulin and colleagues apply structural, biochemical, and biological profiling of two mutants of KRAS, one found most frequently in all cancers (G12D) and one found nearly exclusively in colorectal cancer (A146T). They provide compelling evidence that specific mutations will impart di...

journal_title：Cancer discovery

authors： Hobbs GA,Der CJ

更新日期：2019-06-01 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：: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 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：:Despite recent advances in the use of immunotherapy, only a minority of patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting the DNA damage response (DDR) proteins PARP and checkpoint kinase 1 (CHK1) significantly increased protein and surface expression...

journal_title：Cancer discovery

authors： Sen T,Rodriguez BL,Chen L,Corte CMD,Morikawa N,Fujimoto J,Cristea S,Nguyen T,Diao L,Li L,Fan Y,Yang Y,Wang J,Glisson BS,Wistuba II,Sage J,Heymach JV,Gibbons DL,Byers LA

更新日期：2019-05-01 00:00:00

abstract：:Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A phase III trial is under way to compare its safety and efficacy with that of standard chemotherapy. ...

journal_title：Cancer discovery

authors：

更新日期：2019-05-01 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：:Translational data on chimeric antigen receptor (CAR) T-cell trials indicate that the presence of naïve T cells in the premanufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T-cell distribution from children with solid tu...

journal_title：Cancer discovery

authors： Das RK,Vernau L,Grupp SA,Barrett DM

更新日期：2019-04-01 00:00:00

abstract：:Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC-a dissection of mechanisms underlyin...

journal_title：Cancer discovery

authors： Velcheti V,Wong KK,Saunthararajah Y

更新日期：2019-04-01 00:00:00

abstract：:Electronic cigarettes (e-cigarettes) may be an effective tool for smoking cessation. In a randomized trial, researchers found that 18% of those assigned to use e-cigarettes were smoke-free after a year, compared with 9.9% of those assigned to nicotine replacement therapies such as patches and gum. However, those in th...

journal_title：Cancer discovery

authors：

更新日期：2019-04-01 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：: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：: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：:A recent study suggests that natural killer (NK) cells may play an important role in antitumor response to immune checkpoint inhibitors. Researchers used mouse models to show that NK cells respond to PD-1 and PD-L1 inhibitors, information that could be used to develop immunotherapies that tap NK cells to combat cancer...

journal_title：Cancer discovery

authors：

更新日期：2018-12-01 00:00:00

abstract：:CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced estrogen receptor-positive breast cancer. Mechanisms of CDK4/6 inhibitor resistance have been described preclinically, with limited evidence from clinical samples. We conducted paired baseline and end-of-treatment circulating tumor DNA seq...

journal_title：Cancer discovery

authors： O'Leary B,Cutts RJ,Liu Y,Hrebien S,Huang X,Fenwick K,André F,Loibl S,Loi S,Garcia-Murillas I,Cristofanilli M,Huang Bartlett C,Turner NC

更新日期：2018-11-01 00:00:00

abstract：:The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interact...

journal_title：Cancer discovery

authors： Kalaora S,Wolf Y,Feferman T,Barnea E,Greenstein E,Reshef D,Tirosh I,Reuben A,Patkar S,Levy R,Quinkhardt J,Omokoko T,Qutob N,Golani O,Zhang J,Mao X,Song X,Bernatchez C,Haymaker C,Forget MA,Creasy C,Greenberg P,

更新日期：2018-11-01 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