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Cancer Discovery

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https://www.readbyqxmd.com/read/28729406/tumor-evolution-as-a-therapeutic-target
#1
REVIEW
Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28729405/super-enhancer-analysis-defines-novel-epigenomic-subtypes-of-non-apl-aml-including-an-rar%C3%AE-dependency-targetable-by-sy-1425-a-potent-and-selective-rar%C3%AE-agonist
#2
Michael R McKeown, M Ryan Corces, Matthew L Eaton, Chris Fiore, Emily Lee, Jeremy T Lopez, Mei Wei Chen, Darren Smith, Steven M Chan, Julie L Koenig, Kathryn Austgen, Matt G Guenther, David A Orlando, Jakob Lovén, Christian C Fritz, Ravindra Majeti
We characterized the enhancer landscape of 66 AML patients, identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their super-enhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong super-enhancer at the retinoic acid receptor alpha (RARA) gene locus. Presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene)...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28724523/savolitinib-heads-for-phase-iii-trial-in-prcc
#3
(no author information available yet)
A phase II trial of savolitinib, a MET inhibitor, found that the drug induced partial responses in some patients with papillary renal cell carcinoma and was well tolerated, prompting drug makers Chi-Med and AstraZeneca to launch a phase III study.
July 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710104/genomic-analysis-detects-recurrent-promoter-mutations-in-breast-cancer
#4
(no author information available yet)
Deep sequencing of 360 primary breast tumors identified 9 genes with recurrently mutated promoters.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710103/transcription-elongation-factors-are-potential-targets-in-glioblastoma
#5
(no author information available yet)
JMJD6 promotes transcription pause-release and elongation and glioblastoma cell survival in vivo.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710102/the-telomeric-noncoding-rna-terra-regulates-telomere-stability
#6
(no author information available yet)
TERRA activates the DNA damage response at short telomeres to prevent premature senescence.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710101/superenhancers-drive-neuroblastoma-differentiation-states
#7
(no author information available yet)
Superenhancer-associated transcriptional networks promote neuroblastoma heterogeneity.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710100/biomarker-for-antitumor-immunity-identified
#8
(no author information available yet)
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 cancers.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28710099/nivolumab-plus-ipilimumab-has-antitumor-activity-in-metastatic-rcc
#9
(no author information available yet)
Nivolumab plus ipilimumab achieves durable responses and has manageable safety in metastatic RCC.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687569/bet-degradation-is-more-effective-than-competitive-inhibition-in-t-all
#10
(no author information available yet)
The BET degrader dBET6 induces global BRD4 depletion, whereas JQ1 preferentially affects superenhancers.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687568/a-lymphoreporter-mouse-model-identifies-midkine-as-a-metastasis-driver
#11
(no author information available yet)
Midkine systemically induces neo-lymphangiogenesis via mTOR signaling in patients with melanoma.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687567/correction-nods-for-atezolizumab-and-nivolumab-from-fda
#12
(no author information available yet)
No abstract text is available yet for this article.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687566/the-flt3-inhibitor-gilteritinib-has-activity-in-patients-with-aml
#13
(no author information available yet)
Gilteritinib was well tolerated in a phase I/II dose-escalation and dose-expansion study.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687565/ilf2-is-upregulated-by-1q21-amplification-in-multiple-myeloma
#14
(no author information available yet)
ILF2 induces resistance to DNA-damaging agents by enhancing splicing of DNA damage response mRNAs.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28687564/new-snps-from-testicular-cancer-gwas
#15
(no author information available yet)
Two new genome-wide association studies identify 30 new risk variants for testicular cancer. One study suggests that genes involved in transcription regulation during development and microtubule assembly promote development of the disease. The second study implicates genes involved in mitochondrial metabolism, germ cell maturation, and DNA damage repair.
July 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28667007/the-ragd-gtpase-regulates-mtorc1-activity-to-promote-tumor-growth
#16
(no author information available yet)
MiT/TFE transcription factors directly upregulate RagD, which activates mTORC1 to support tumor growth.
June 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28667006/whole-genome-and-epigenomic-landscapes-of-etiologically-distinct-subtypes-of-cholangiocarcinoma
#17
Apinya Jusakul, Ioana Cutcutache, Chern Han Yong, Jing Quan Lim, Mi Ni Huang, Nisha Padmanabhan, Vishwa Nellore, Sarinya Kongpetch, Alvin Wei Tian Ng, Ley Moy Ng, Su Pin Choo, Swe Swe Myint, Raynoo Thanan, Sanjanaa Nagarajan, Weng Khong Lim, Cedric Chuan Young Ng, Arnoud Boot, Mo Liu, Choon Kiat Ong, Vikneswari Rajasegaran, Stefanus Lie, Alvin Soon Tiong Lim, Tse Hui Lim, Jing Tan, Jia Liang Loh, John R McPherson, Narong Khuntikeo, Vajaraphongsa Bhudhisawasdi, Puangrat Yongvanit, Sopit Wongkham, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Satoshi Yamasaki, Pierce K H Chow, Alexander Yaw Fui Chung, London Lucien Peng Jin Ooi, Kiat Hon Lim, Simona Dima, Dan G Duda, Irinel Popescu, Philippe Broet, Sen-Yung Hsieh, Ming-Chin Yu, Aldo Scarpa, Jiaming Lai, Di-Xian Luo, Andre Lopes Carvalho, André Luiz Vettore, Hyungjin Rhee, Young Nyun Park, Ludmil Alexandrov, Raluca Gordan, Steven G Rozen, Tatsuhiro Shibata, Chawalit Pairojkul, Bin Tean Teh, Patrick Tan
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements...
June 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28667005/mtorc2-regulates-the-cystine-glutamate-antiporter-xct
#18
(no author information available yet)
mTORC2 controls glutamate and glutathione metabolism in cancer cells by phosphorylating xCT.
June 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28667004/bap1-and-pten-stabilize-ip3r3-to-promote-ca-2-mediated-apoptosis
#19
(no author information available yet)
BAP1 and PTEN prevent IP3R3 degradation, increasing Ca(2+) flux and apoptosis to suppress tumor growth.
June 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28667003/de-novo-methylation-halts-pd-1-blockade-mediated-t-cell-revitalization
#20
(no author information available yet)
Heritable de novo methylation programs induce the terminal differentiation of exhausted T cells.
June 30, 2017: Cancer Discovery
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