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Cancer Discovery

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https://www.readbyqxmd.com/read/28642250/widespread-genomic-testing-deemed-feasible
#1
(no author information available yet)
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 changes in their tumor lived longer than those who lacked a so-called actionable mutation.
June 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28642249/unc-cancer-center-director-to-lead-nci
#2
(no author information available yet)
President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts.
June 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28634245/targeting-nectin-4-in-bladder-cancer
#3
(no author information available yet)
Preliminary findings from a phase I clinical trial indicate that enfortumab vedotin, an investigational antibody-drug conjugate targeting nectin-4, shows considerable efficacy in metastatic urothelial carcinoma. Robust responses were seen even among patients with disease progression on platinum chemotherapy and/or immune checkpoint blockade.
June 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28630051/dna-damage-and-repair-biomarkers-of-immunotherapy-response
#4
REVIEW
Kent W Mouw, Michael S Goldberg, Panagiotis A Konstantinopoulos, Alan D D'Andrea
DNA-damaging agents are widely used in clinical oncology and exploit deficiencies in tumor DNA repair. Given the expanding role of immune checkpoint blockade as a therapeutic strategy, the interaction of tumor DNA damage with the immune system has recently come into focus, and it is now clear that the tumor DNA repair landscape has an important role in driving response to immune checkpoint blockade. Here, we summarize the mechanisms by which DNA damage and genomic instability have been found to shape the antitumor immune response and describe clinical efforts to use DNA repair biomarkers to guide use of immune-directed therapies...
June 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626036/treating-er-breast-cancer-with-cdk4-6-inhibitors
#5
(no author information available yet)
Data from the MONARCH2, PALOMA-1, and TREnd trials strongly support using CDK4/6 inhibitors alongside standard endocrine therapy for advanced ER-positive breast cancer. Including these targeted agents not only improves progression-free survival but may reverse acquired resistance to hormone treatment.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626035/cyclin-d3-cdk6-has-a-metabolic-prosurvival-role-in-t-all
#6
(no author information available yet)
Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626034/drug-induced-epigenetic-reprogramming-promotes-drug-resistance
#7
(no author information available yet)
Drug treatment causes resistance in cells with transiently high expression of drug resistance markers.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626033/dabrafenib-plus-trametinib-achieves-overall-and-intracranial-responses
#8
(no author information available yet)
Dabrafenib plus trametinib achieves intracranial responses in BRAF-mutant melanoma brain metastases.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626032/a-subset-of-gene-promoters-exhibit-both-promoter-and-enhancer-activity
#9
(no author information available yet)
Approximately 2%-3% of gene promoters also display distal enhancer activity (termed Epromoters).
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28626031/mismatch-repair-deficiency-confers-sensitivity-to-checkpoint-blockade
#10
(no author information available yet)
PD-1 blockade with pembrolizumab achieves responses in 53% of patients with MMR-deficient tumors.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619981/ibrutinib-unmasks-critical-role-of-bruton-tyrosine-kinase-in-primary-cns-lymphoma
#11
Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Daniel Rohle, Marc K Rosenblum, Agnes Viale, Viviane Tabar, Cameron W Brennan, Igor T Gavrilovic, Thomas J Kaley, Craig Nolan, Antonio M P Omuro, Elena Pentsova, Alissa A Thomas, Elina Tsyvkin, Ariela Noy, M Lia Palomba, Paul A Hamlin, Craig Sauter, Craig H Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C Lallana, Vaios Hatzoglou, Anne S Reiner, Philip Gutin, Jason T Huse, Katherine Panageas, Thomas G Graeber, Nikolaus Schultz, Lisa M DeAngelis, Ingo K Mellinghoff
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with Nuclear factor kappa B (NF-κB). The role of BTK in primary CNS lymphoma (PCNSL) is unknown. We performed a Phase 1 clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS Lymphoma. Clinical responses to ibrutinib occurred in 10/13 (77%) PCNSL patients, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of Caspase Recruitment Domain Family Member 11, a known ibrutinib resistance mechanism...
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619980/pan-cancer-analysis-pinpoints-targets-in-pi3k-pathway
#12
(no author information available yet)
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 the pathway and may point to new drug targets.
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619979/modeling-cancer-mutations-in-3-d
#13
(no author information available yet)
Researchers from the Wellcome Trust Sanger Institute have launched COSMIC-3D, a tool that allows scientists to explore how cancer mutations affect the structure and function of more than 8,000 human proteins. They hope COSMIC-3D, which is freely available on the web, will facilitate the design of new cancer drugs.
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28615281/macrophages-promote-resistance-to-checkpoint-inhibitors
#14
(no author information available yet)
A study in mice suggests that macrophages produce resistance to checkpoint inhibitors by removing anti-PD-1 antibodies from T cells. Fcγ receptors on macrophages bind to the Fc domain on the antibodies. Blocking this interaction with other antibodies produced dramatic tumor shrinkage in mice.
June 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28607097/correction-adaptive-reprogramming-of-de-novo-pyrimidine-synthesis-is-a-metabolic-vulnerability-in-triple-negative-breast-cancer
#15
(no author information available yet)
No abstract text is available yet for this article.
June 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28600468/bcr-loss-reduces-the-fitness-of-myc-driven-lymphoma-cells
#16
(no author information available yet)
BCR-proficient lymphoma cells exhibit a competitive growth advantage in vitro and in vivo.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28600467/the-structure-of-abcg2-provides-insight-into-multidrug-resistance
#17
(no author information available yet)
The ABCG2 structure reveals the multidrug-binding pocket and suggests a multidrug transport mechanism.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28600466/alectinib-superior-to-crizotinib-for-alk-nsclc
#18
(no author information available yet)
Findings from the global phase III ALEX trial unequivocally show that alectinib is superior to crizotinib as first-line therapy for ALK+ non-small cell lung cancer. Alectinib more than doubled progression-free survival, significantly reduced the incidence of brain and CNS metastases, and should be considered the new standard of care.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28600465/loss-of-vhl-trp53-and-rb1-induces-clear-cell-renal-carcinoma-in-mice
#19
(no author information available yet)
An autochthonous mouse model of clear cell renal cell carcinoma (ccRCC) recapitulates the human disease.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28600464/biallelic-mutations-in-trip13-increase-the-risk-of-wilms-tumor
#20
(no author information available yet)
Mutations resulting in loss of TRIP13 expression induce chromosome missegregation and SAC impairment.
June 9, 2017: Cancer Discovery
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