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Cancer Discovery

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https://www.readbyqxmd.com/read/29463507/bmi-can-underestimate-breast-cancer-risk
#1
(no author information available yet)
New findings suggest that postmenopausal women with high levels of body fat are at increased risk of ER-positive breast cancer, even if their body mass index is within the normal range. If confirmed, these results would put many more women at elevated risk for breast cancer than was previously thought, with implications for the way that healthy-weight women should be counseled to reduce their health risks.
February 20, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29459439/apalutamide-approved-for-certain-prostate-cancers
#2
(no author information available yet)
The FDA approved the antiandrogen apalutamide for the treatment of men with nonmetastatic, castration-resistant prostate cancer, the first drug for these patients greenlighted by the agency. Data from the definitive trial of apalutamide, presented at the 2018 Genitourinary Cancers Symposium, showed that the drug prolonged metastasis-free survival by more than 2 years compared with placebo. Data on the related drug enzalutamide, also presented at the symposium, showed that that drug led to dramatic improvements in metastasis-free survival, too...
February 19, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453241/the-pi3k%C3%AE-inhibitor-alpelisib-has-activity-in-pik3ca-altered-tumors
#3
(no author information available yet)
The PI3Kα inhibitor alpelisib achieved a 58.2% disease control rate in PIK3CA -altered solid tumors.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453240/arvinas-pfizer-team-up-on-protacs
#4
(no author information available yet)
Biotechnology startup Arvinas is developing proteolysis-targeting chimeras (PROTAC) that combat cancer by degrading disease-causing proteins. The company's first PROTACs will target prostate and breast cancers, and a recent deal with Pfizer will allow Arvinas to develop PROTACs for other cancer types.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453239/a-next-generation-chimeric-antigen-receptor-induces-jak-stat-signaling
#5
(no author information available yet)
CAR-T cells designed to activate JAK-STAT signaling show enhanced persistence and antitumor activity.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453238/natural-killer-cells-recruit-dendritic-cells-to-promote-antitumor-immunity
#6
(no author information available yet)
Natural killer (NK) cells recruit conventional type 1 dendritic cells (cDC1) to the tumor microenvironment.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453237/asparagine-bioavailability-drives-breast-cancer-metastasis
#7
(no author information available yet)
Asparagine depletion reduces breast cancer invasion and metastasis without affecting primary tumor growth.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453236/dnmt3a-dna-binding-residues-provide-specificity-for-cpg-dna-methylation
#8
(no author information available yet)
DNMT3A-DNMT3L-DNA crystal structures provide a mechanism for DNMT3A methyltransferase activity.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29449271/targeted-therapies-for-targeted-populations-anti-egfr-treatment-for-egfr-amplified-gastroesophageal-adenocarcinoma
#9
Steven B Maron, Lindsay Alpert, Heewon A Kwak, Samantha Lomnicki, Leah Chase, David Xu, Emily O'Day, Rebecca J Nagy, Richard B Lanman, Fabiola Cecchi, Todd Hembrough, Alexa Schrock, John Hart, Shu-Yuan Xiao, Namrata Setia, Daniel V T Catenacci
Previous anti-EGFR trials in unselected gastroesophageal adenocarcinoma (GEA) patients were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven pts received >1 dose of treatment: three first line FOLFOX plus ABT-806, one second line FOLFIRI plus cetuximab, and three third/fourth line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months...
February 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29440173/canine-research-to-benefit-humans-and-dogs-alike
#10
(no author information available yet)
The Jackson Laboratory recently launched the Tallwood Canine Cancer Research Initiative, in which tumor samples from dogs will be collected to create patient-derived xenografts in mice. These models, and their accompanying genome sequences, can then be shared with researchers around the world. The initiative's goal is to learn more about the biology of human cancers through comparative genomic analyses.
February 13, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29439154/tumorigenic-colonic-bacteria-may-promote-early-neoplasia
#11
(no author information available yet)
Colonic biofilms may accelerate tumorigenesis in patients with familial adenomatous polyposis (FAP).
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29439153/ar-inhibition-achieves-responses-in-ar-triple-negative-breast-cancer
#12
(no author information available yet)
The AR inhibitor enzalutamide achieved responses in patients with advanced TNBC in a phase II trial.
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29439152/slfn11-blocks-dna-replication-independently-of-atr-activity
#13
(no author information available yet)
SLFN11 inhibits replication in response to DNA damage or cell cycle checkpoint inhibition.
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29439151/-mycn-amplification-promotes-enhancer-invasion-in-neuroblastoma
#14
(no author information available yet)
Excess MYCN binds noncanonical enhancers as well as promoters to drive tumor-specific gene expression.
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29439150/myelodysplastic-syndrome-splicing-factor-mutations-induce-r-loops
#15
(no author information available yet)
Mutations in SRSF2 and U2AF35 trigger replication stress and ATR activation via R-loop formation.
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431699/combined-braf-egfr-and-mek-inhibition-in-patients-with-brafv600e-mutant-colorectal-cancer
#16
Ryan B Corcoran, Thierry Andre, Chloe E Atreya, Jan H M Schellens, Takayuki Yoshino, Johanna C Bendell, Antoine Hollebecque, Autumn J McRee, Salvatore Siena, Gary Middleton, Kei Muro, Michael S Gordon, Josep Tabernero, Rona Yaeger, Peter J O'Dwyer, Yves Humblet, Filip De Vos, A Scott Jung, Jan C Brase, Savina Jaeger, Severine Bettinger, Bijoyesh Mookerjee, Fatima Rangwala, Eric Van Cutsem
Although BRAF inhibitor monotherapy yields response rates >50% in BRAFV600-mutant melanoma, only ~5% with BRAFV600E colorectal cancer (CRC) respond. Preclinical studies suggest that lack of efficacy in BRAFV600E CRC is due to adaptive feedback reactivation of MAPK signaling, often mediated by EGFR. This clinical trial evaluated BRAF and EGFR inhibition with dabrafenib (D) + panitumumab (P) ± MEK inhibition with trametinib (T) to achieve greater MAPK suppression and improved efficacy in 142 patients with BRAFV600E CRC...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431698/mef2c-phosphorylation-is-required-for-chemotherapy-resistance-in-acute-myeloid-leukemia
#17
Fiona C Brown, Eric Still, Richard P Koche, Christina Y Yim, Sumiko Takao, Paolo Cifani, Casie Reed, Shehana Gunasekera, Scott B Ficarro, Peter Romanienko, Willie Mark, Craig McCarthy, Elisa de Stanchina, Mithat Gonen, Venkatraman Seshan, Patrick Bhola, Conor O'Donnell, Barbara Spitzer, Crystal Stutzke, Vincent-Philippe Lavallée, Josée Hébert, Andrei V Krivstov, Ari Melnick, Elisabeth M Paietta, Martin S Tallman, Anthony Letai, Guy Sauvageau, Gayle Pouliot, Ross Levine, Jarrod A Marto, Scott A Armstrong, Alex Kentsis
In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2c S222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, and induced by MARK kinases in cells...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431697/convergent-therapeutic-strategies-to-overcome-the-heterogeneity-of-acquired-resistance-in-brafv600e-colorectal-cancer
#18
Mehlika Hazar-Rethinam, Marianna Kleyman, G Celine Han, David Liu, Leanne G Ahronian, Heather A Shahzade, Lifeng Chen, Aparna R Parikh, Jill N Allen, Jeffrey W Clark, Eunice L Kwak, Jason E Faris, Janet E Murphy, Theodore S Hong, Emily E Van Seventer, Brandon Nadres, Catriona B Hong, Joseph M Gurski, Nicholas A Jessop, Dora Dias-Santagata, A John Iafrate, Eliezer M Van Allen, Ryan B Corcoran
Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from BRAFV600E colorectal cancer patients receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a novel pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivo...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431696/e-cigarette-report-reveals-research-gaps
#19
(no author information available yet)
In a comprehensive analysis of existing studies, the U.S. National Academies of Sciences, Engineering, and Medicine concluded that electronic cigarettes are addictive, though less toxic than conventional cigarettes. The report also identified key areas for future research, including smoking cessation, adolescent use, and long-term health effects.
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431695/advancing-cancer-screening-with-liquid-biopsies
#20
(no author information available yet)
A new liquid biopsy technique, CancerSEEK, that evaluates tumor mutations and cancer-linked proteins can detect 70% of cancers in patients who have one of eight tumor types. The technique can pinpoint the location of a tumor in 68% of cases. However, its sensitivity drops off at earlier disease stages.
February 5, 2018: Cancer Discovery
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