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Cancer Discovery

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https://www.readbyqxmd.com/read/28087574/stabilization-of-wild-type-mll-displaces-oncogenic-mll-fusion-proteins
#1
(no author information available yet)
IL1 signaling promotes degradation of wild-type MLL to enhance MLL leukemia cell proliferation.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28087573/fto-mediated-mrna-demethylation-drives-leukemogenesis
#2
(no author information available yet)
The mRNA demethylase FTO promotes leukemogenesis and inhibits ATRA-mediated differentiation.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28087572/the-kras-membrane-anchor-regulates-signaling-through-lipid-specificity
#3
(no author information available yet)
KRAS lipid specificity controls signaling and is not determined solely by electrostatic attraction.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28087571/pancreatic-tumors-exhibit-enhanced-extracellular-protein-catabolism
#4
(no author information available yet)
PDACs gain necessary amino acids via macropinocytosis and degradation of extracellular proteins.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28087570/tissues-from-young-mice-and-patients-are-primed-for-apoptosis
#5
(no author information available yet)
Brain, heart, and kidney tissues from young mice are highly susceptible to treatment-induced apoptosis.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28077436/project-genie-goes-public
#6
(no author information available yet)
The American Association for Cancer Research's Project Genomics Evidence Neoplasia Information Exchange released almost 19,000 deidentified genomic records collected from patients with cancer who were treated at one of eight renowned medical centers. One of the largest pools of genomic information ever made publicly accessible, it includes data on 59 types of cancer.
January 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28077435/blu-285-dcc-2618-show-activity-against-gist
#7
(no author information available yet)
Tyrosine kinase inhibitors may initially control gastrointestinal stromal tumors, but most patients eventually experience disease progression due to activation loop mutations, which are resistant to approved drugs. However, phase I trials suggest that the cancer is sensitive to two new agents: BLU-285 and DCC-2618. In addition, liquid biopsies, which were used to follow patients during the trials, may be valuable tools in tracking disease progression and assessing tumor heterogeneity.
January 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069571/apc-c-dysfunction-limits-excessive-cancer-chromosomal-instability
#8
Laurent Sansregret, James O Patterson, Sally Dewhurst, Carlos López-García, André Koch, Nicholas McGranahan, William Chong Hang Chao, David J Barry, Andrew Rowan, Rachael Instrell, Stuart Horswell, Michael Way, Michael Howell, Martin R Singleton, René H Medema, Paul Nurse, Mark Petronczki, Charles Swanton
: Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069570/anti-cd22-car-therapy-leads-to-all-remissions
#9
(no author information available yet)
In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069569/the-crebbp-acetyltransferase-is-a-haploinsufficient-tumor-suppressor-in-b-cell-lymphoma
#10
Jiyuan Zhang, Sofija Vlasevska, Victoria A Wells, Sarah Nataraj, Antony B Holmes, Romain Duval, Stefanie N Meyer, Tongwei Mo, Katia Basso, Paul K Brindle, Shafinaz Hussein, Riccardo Dalla-Favera, Laura Pasqualucci
Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal-center (GC) derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062478/samhd1-limits-the-effectiveness-of-cytarabine-in-aml
#11
(no author information available yet)
The dNTP triphosphohydrolase SAMHD1 decreases cytarabine (Ara-C) cytotoxicity in AML cells.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062477/imgn853-is-active-in-patients-with-fr%C3%AE-positive-ovarian-cancer
#12
(no author information available yet)
A FRα-targeting antibody-drug conjugate induces responses in patients with platinum-resistant tumors.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062476/arid1a-deficiency-promotes-colorectal-cancer-via-enhancer-dysregulation
#13
(no author information available yet)
ARID1A loss disrupts SWI/SNF targeting to enhancers to alter gene expression and drive colorectal cancer.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062475/the-cytoplasmic-sensor-nlrc3-inhibits-mtor-signaling-in-tumors
#14
(no author information available yet)
NLRC3 negatively regulates PI3K-mTOR signaling to inhibit colon tumorigenesis.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062474/smarcb1-mutations-disrupt-enhancer-activity-in-rhabdoid-tumors
#15
(no author information available yet)
Loss of the SWI/SNF subunit SMARCB1 disrupts enhancer activation but retains superenhancer activity.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28057616/rucaparib-approved-for-ovarian-cancer
#16
(no author information available yet)
The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test. The agency also gave a nod to the FoundationFocus CDxBRCA test to detect BRCA alterations.
January 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28034880/polyclonal-secondary-fgfr2-mutations-drive-acquired-resistance-to-fgfr-inhibition-in-patients-with-fgfr2-fusion-positive-cholangiocarcinoma
#17
Lipika Goyal, Supriya K Saha, Leah Y Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G Ahronian, Jochen K Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E Van Seventer, Joseph M Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P Ryan, James R Stone, A John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B Corcoran, Nabeel Bardeesy, Andrew X Zhu
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases...
December 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#18
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William H Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
December 28, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28007947/ppp2r3b-is-a-sex-linked-melanoma-tumor-suppressor-gene
#19
(no author information available yet)
PPP2R3B dosage is associated with sex chromosome status and outcome in melanoma.
December 22, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28007946/-cures-act-signed-into-law
#20
(no author information available yet)
President Obama has signed the 21st Century Cures Act into law. The bill provides $4.8 billion to three key health-related measures of the outgoing administration: the Beau Biden Cancer Moonshot, the Precision Medicine Initiative, and the BRAIN initiative.
December 22, 2016: Cancer Discovery
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