ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.

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：:Based on the results of two large international randomized trials, the FDA approved the anti-PD-L1 agent atezolizumab in October. It is the first PD-L1 inhibitor approved for use in patients with metastatic non-small cell lung cancer that has advanced in spite of treatment with platinum-based chemotherapy. ...

journal_title：Cancer discovery

authors：

更新日期：2016-12-01 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：:Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer. Improved progression-free survival was seen regardless of the presence or absence of germline BRCA mutations, or o...

journal_title：Cancer discovery

authors：

更新日期：2016-12-01 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：:Circadian rhythms integrate many physiological pathways, helping organisms to align the timing of various internal processes to daily cycles in the external environment. Disrupted circadian rhythmicity is a prominent feature of modern society, and has been designated as a probable carcinogen. Here, we review multiple ...

journal_title：Cancer discovery

authors： Pariollaud M,Lamia KA

更新日期：2020-10-01 00:00:00

abstract：:Researchers identified a small molecule that stimulates the production of stem cells in umbilical cord blood, potentially expanding treatment options for adults with hematologic cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2014-12-01 00:00:00

abstract：:According to the final analysis of CLEOPATRA, first-line treatment with pertuzumab plus trastuzumab and docetaxel significantly improves overall survival for patients with HER2-positive metastatic breast cancer. As such, dual HER2 blockade plus chemotherapy should be the standard of care in this setting, researchers s...

journal_title：Cancer discovery

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更新日期：2014-12-01 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：UNLABELLED:Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy, and its molecular basis is poorly understood. We previously demonstrated that opioid binding protein cell adhesion molecule (OPCML) was frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppress...

journal_title：Cancer discovery

authors： McKie AB,Vaughan S,Zanini E,Okon IS,Louis L,de Sousa C,Greene MI,Wang Q,Agarwal R,Shaposhnikov D,Wong JL,Gungor H,Janczar S,El-Bahrawy M,Lam EW,Chayen NE,Gabra H

更新日期：2012-02-01 00:00:00

abstract：:In the setting of recent exciting clinical results and numerous ongoing trials, Piotrowska and colleagues explore mechanisms of acquired resistance to the mutant-specific EGFR inhibitor rociletinib, and demonstrate that loss of T790M, EGFR amplification, and small-cell transformation are all clinically relevant mechan...

journal_title：Cancer discovery

authors： Ichihara E,Lovly CM

更新日期：2015-07-01 00:00:00

abstract：:The APOBEC proteins fight off viruses by editing their genomes. A deletion that removes one of the proteins produces large numbers of mutations in the human genome, potentially leading to cancer. ...

journal_title：Cancer discovery

authors：

更新日期：2014-07-01 00:00:00

abstract：:Although comprehensive genomic screening has not yet become routine when treating patients with cancer, widespread testing in those with advanced, refractory disease is feasible, according to the ongoing ProfiLER study. The study also found that patients who subsequently received a treatment matched to the genetic cha...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 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：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：: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：:CD14+CD16-HLA-DRhi monocyte frequency was linked to response to anti-PD-1 in patients with melanoma. ...

journal_title：Cancer discovery

authors：

更新日期：2018-03-01 00:00:00

abstract：:An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use ...

journal_title：Cancer discovery

authors： MacConaill LE,Van Hummelen P,Meyerson M,Hahn WC

更新日期：2011-09-01 00:00:00

abstract：:Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti-PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 pati...

journal_title：Cancer discovery

authors： Shin DS,Zaretsky JM,Escuin-Ordinas H,Garcia-Diaz A,Hu-Lieskovan S,Kalbasi A,Grasso CS,Hugo W,Sandoval S,Torrejon DY,Palaskas N,Rodriguez GA,Parisi G,Azhdam A,Chmielowski B,Cherry G,Seja E,Berent-Maoz B,Shintaku IP,L

更新日期：2017-02-01 00:00:00

abstract：:Preliminary results from an ongoing phase I clinical trial in China suggest that chimeric antigen receptor T cells engineered to home in on a protein called BCMA may be a potent therapeutic option for multiple myeloma. The therapy was well tolerated and induced complete, durable responses in patients with relapsed/ref...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 00:00:00

abstract：:The clinical success of EGF receptor (EGFR) inhibitors in patients with lung cancer is limited by the inevitable development of treatment resistance. Two reports in this issue of Cancer Discovery uncover additional mechanisms by which EGFR-mutant lung cancers escape from EGFR kinase inhibitor treatment. These findings...

journal_title：Cancer discovery

authors： Blakely CM,Bivona TG

更新日期：2012-10-01 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：: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

authors：

更新日期：2016-10-01 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：: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：: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：UNLABELLED:Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell cul...

journal_title：Cancer discovery

authors： Bose R,Kavuri SM,Searleman AC,Shen W,Shen D,Koboldt DC,Monsey J,Goel N,Aronson AB,Li S,Ma CX,Ding L,Mardis ER,Ellis MJ

更新日期：2013-02-01 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：: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：:According to findings of a study in the Journal of the National Cancer Institute, people with a single-nucleotide polymorphism on chromosome 8q24 who regularly use aspirin can cut their risk of colorectal cancer by about half. ...

journal_title：Cancer discovery

authors：

更新日期：2014-03-01 00:00:00