Oncogenes Induce Replication Stress via Intragenic Replication Origins.

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：: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：: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：: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：:CD14+CD16-HLA-DRhi monocyte frequency was linked to response to anti-PD-1 in patients with melanoma. ...

journal_title：Cancer discovery

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更新日期：2018-03-01 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

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更新日期：2019-05-01 00:00:00

abstract：:The TIGIT inhibitor tiragolumab, alone or in combination with the PD-L1 inhibitor atezolizumab, may be effective against solid cancers. In phase I and II trials, the agent achieved statistically significant results in multiple solid malignancies-most notably non-small cell lung cancer. ...

journal_title：Cancer discovery

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更新日期：2020-08-01 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：:BRAF inhibitors stabilize a closed, rigid RAF kinase conformation that facilitates dimerization. ...

journal_title：Cancer discovery

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更新日期：2013-07-01 00:00:00

abstract：:A new study of all 32 cancer types in The Cancer Genome Atlas identifies genomic alterations that increase the activity of the PI3K/AKT/mTOR pathway. The study, which combines mutation data with measures of protein levels and phosphorylation status, suggests that mutations in IDH1, VHL, and STK11 promote activation of...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 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：:MYC is implicated in the development and progression of pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumor development has been difficult to define. We used modestly elevated expression of human MYC, driven from the Rosa26 locus, to investigate the pancreatic phenotypes arisin...

journal_title：Cancer discovery

authors： Muthalagu N,Monteverde T,Raffo-Iraolagoitia X,Wiesheu R,Whyte D,Hedley A,Laing S,Kruspig B,Upstill-Goddard R,Shaw R,Neidler S,Rink C,Karim SA,Gyuraszova K,Nixon C,Clark W,Biankin AV,Carlin LM,Coffelt SB,Sansom OJ,

更新日期：2020-06-01 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：UNLABELLED:Indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have entered clinical trials for cancer treatment based on preclinical studies, indicating that they can defeat immune escape and broadly enhance other therapeutic modalities. However, clear genetic evidence of the impact of IDO on tumorigenesis in physiolo...

journal_title：Cancer discovery

authors： Smith C,Chang MY,Parker KH,Beury DW,DuHadaway JB,Flick HE,Boulden J,Sutanto-Ward E,Soler AP,Laury-Kleintop LD,Mandik-Nayak L,Metz R,Ostrand-Rosenberg S,Prendergast GC,Muller AJ

更新日期：2012-08-01 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：:The FDA has approved pembrolizumab for adults and children with classical Hodgkin lymphoma whose disease is refractory to or has relapsed after at least three prior therapies. The approval marks the first time that a PD-1 inhibitor has been indicated for blood cancers-and for children. ...

journal_title：Cancer discovery

authors：

更新日期：2017-05-01 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：UNLABELLED:Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have ...

journal_title：Cancer discovery

authors： Hidalgo M,Amant F,Biankin AV,Budinská E,Byrne AT,Caldas C,Clarke RB,de Jong S,Jonkers J,Mælandsmo GM,Roman-Roman S,Seoane J,Trusolino L,Villanueva A

更新日期：2014-09-01 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：:The new iRECIST guideline-developed in consultation with academics, drug companies, and regulatory authorities-provides a standardized approach to assessing whether patients' disease improves, stays the same, or worsens in trials of immunotherapeutics, agents that can trigger different response patterns from other kin...

journal_title：Cancer discovery

authors：

更新日期：2017-05-01 00:00:00

abstract：:We performed cytosine methylation sequencing on genetically diverse patients with acute myeloid leukemia (AML) and found leukemic DNA methylation patterning is primarily driven by nonpromoter regulatory elements and CpG shores. Enhancers displayed stronger differential methylation than promoters, consisting predominan...

journal_title：Cancer discovery

authors： Glass JL,Hassane D,Wouters BJ,Kunimoto H,Avellino R,Garrett-Bakelman FE,Guryanova OA,Bowman R,Redlich S,Intlekofer AM,Meydan C,Qin T,Fall M,Alonso A,Guzman ML,Valk PJM,Thompson CB,Levine R,Elemento O,Delwel R,Meln

更新日期：2017-08-01 00:00:00

abstract：:A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 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：: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：UNLABELLED:Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings ...

journal_title：Cancer discovery

authors： Beltran H,Rickman DS,Park K,Chae SS,Sboner A,MacDonald TY,Wang Y,Sheikh KL,Terry S,Tagawa ST,Dhir R,Nelson JB,de la Taille A,Allory Y,Gerstein MB,Perner S,Pienta KJ,Chinnaiyan AM,Wang Y,Collins CC,Gleave ME,Demi

更新日期：2011-11-01 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

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更新日期：2017-09-01 00:00:00

abstract：:Nuclear hormone receptor targeting suppresses melanoma progression in diverse preclinical models. ...

journal_title：Cancer discovery

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更新日期：2014-05-01 00:00:00

abstract：:Researchers have identified a new compound, OTS964, that blocks cytokinesis. Injections of the compound eliminated human lung tumors that had been transplanted into mice. Clinical trials of OTS964 may start next year. ...

journal_title：Cancer discovery

authors：

更新日期：2015-01-01 00:00:00

abstract：:Amid concerns over the spread of COVID-19, oncology practices have "gone virtual," with video appointments scheduled for any service that does not require diagnostic testing or treatment. ...

journal_title：Cancer discovery

authors：

更新日期：2020-06-01 00:00:00

abstract：:Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of...

journal_title：Cancer discovery

authors： Saura C,Roda D,Roselló S,Oliveira M,Macarulla T,Pérez-Fidalgo JA,Morales-Barrera R,Sanchis-García JM,Musib L,Budha N,Zhu J,Nannini M,Chan WY,Sanabria Bohórquez SM,Meng RD,Lin K,Yan Y,Patel P,Baselga J,Tabernero J,

更新日期：2017-01-01 00:00:00