Patient-derived xenograft models: an emerging platform for translational cancer research.

abstract：:Drug resistance poses a great challenge to targeted cancer therapies. In Hedgehog pathway-dependent cancers, the scope of mechanisms enabling resistance to SMO inhibitors is not known. Here, we performed a transposon mutagenesis screen in medulloblastoma and identified multiple modes of resistance. Surprisingly, mutat...

journal_title：Cancer discovery

authors： Zhao X,Pak E,Ornell KJ,Pazyra-Murphy MF,MacKenzie EL,Chadwick EJ,Ponomaryov T,Kelleher JF,Segal RA

更新日期：2017-12-01 00:00:00

abstract：:A study shows that analyzing the protein contents of exosomes and related extracellular vesicles can distinguish tumors from nearby noncancerous tissue, and profiling extracellular vesicle proteins obtained from plasma may also reveal cancer type. The results support using vesicle proteins for liquid biopsies. ...

journal_title：Cancer discovery

authors：

更新日期：2020-11-01 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：: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：: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：:In the setting of recent exciting clinical results and numerous ongoing trials, Gainor and colleagues explored mechanisms of acquired resistance to first- and second-generation ALK inhibitors in ALK-rearranged non-small cell lung cancer and found that an increased frequency and distinct spectrums of resistance mutatio...

journal_title：Cancer discovery

authors： Qiao H,Lovly CM

更新日期：2016-10-01 00:00:00

abstract：:Adding a PI3K inhibitor to anti-estrogen receptor therapy may be a viable treatment option for women with advanced hormone receptor-positive breast cancer that becomes resistant to endocrine therapy, according to findings from the phase III BELLE-2 trial, presented at the 2015 San Antonio Breast Cancer Symposium. ...

journal_title：Cancer discovery

authors：

更新日期：2016-02-01 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：:The FDA approved 22 novel drugs in 2016, down from 45 in 2015. Four of the new therapies are for cancer treatment, and two are for cancer diagnosis. ...

journal_title：Cancer discovery

authors：

更新日期：2017-02-01 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：:A new mathematical model finds that tumor neoantigen quality trumps quantity when it comes to predicting response to immunotherapy and the likelihood of long-term survival among patients with cancer. ...

journal_title：Cancer discovery

authors：

更新日期：2018-01-01 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：: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

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更新日期：2016-10-01 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 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：:Somatic ERBB3 hot-spot mutations promote oncogenic signaling in a subset of human tumors. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：:Gilead announced plans in July to pay $300 million for a 49.9% stake in Tizona Therapeutics, with the option to buy the rest of the company for $1.25 billion. Whether Gilead follows through with the acquisition will hinge on how well Tizona's investigational HLA-G inhibitor, TTX-080, fares in early-stage clinical tria...

journal_title：Cancer discovery

authors：

更新日期：2020-10-01 00:00:00

abstract：:A phase III trial testing nivolumab to treat advanced melanoma was stopped early due to improved overall survival compared with standard chemotherapy. ...

journal_title：Cancer discovery

authors：

更新日期：2014-09-01 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：: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：:Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-h...

journal_title：Cancer discovery

authors： Yap TA,Tan DSP,Terbuch A,Caldwell R,Guo C,Goh BC,Heong V,Haris NRM,Bashir S,Drew Y,Hong DS,Meric-Bernstam F,Wilkinson G,Hreiki J,Wengner AM,Bladt F,Schlicker A,Ludwig M,Zhou Y,Liu L,Bordia S,Plummer R,Lagkadin

更新日期：2020-09-28 00:00:00

abstract：:The FDA has approved the small-molecule inhibitor midostaurin in combination with chemotherapy to treat acute myeloid leukemia. It is the first approved drug for the disease that specifically targets FLT3 mutations, which occur in about a quarter of all AML cases and are associated with particularly poor outcomes. ...

journal_title：Cancer discovery

authors：

更新日期：2017-07-01 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：UNLABELLED:The relationships between telomerase and telomeres represent attractive targets for new anticancer agents. Here, we report that the nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG) is recognized by telomerase and is incorporated into de novo-synthesized telomeres. This results in modified telomeres, ...

journal_title：Cancer discovery

authors： Mender I,Gryaznov S,Dikmen ZG,Wright WE,Shay JW

更新日期：2015-01-01 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：: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：:The appearance of a mutant androgen receptor, AR(F876L), in prostate cancer cells chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist to agonist receptor function, undermining the potential long-term effectiveness of these second-generation antiandrogen drugs. ...

journal_title：Cancer discovery

authors： Nelson WG,Yegnasubramanian S

更新日期：2013-09-01 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：: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：: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