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Cancer Discovery

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https://www.readbyqxmd.com/read/28821506/crizotinib-has-antitumor-activity-in-alk-positive-alcl-and-imt
#1
(no author information available yet)
Crizotinib has an overall response rate of 90% in ALCL and 86% in IMT at the recommended phase II dose.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28821505/tmprss2-erg-alters-the-cis-regulatory-landscape-and-activates-notch
#2
(no author information available yet)
In TMPRSS2-ERG-positive prostate tumors, ERG establishes new clusters of regulatory elements (CORE).
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28821504/pon2-promotes-glucose-uptake-to-support-pdac-growth-and-metastasis
#3
(no author information available yet)
PON2 promotes GLUT1-mediated glucose transport, is upregulated in PDAC, and is required for PDAC growth.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28821503/anti-ctla4-and-anti-pd-1-act-on-distinct-t-cell-populations
#4
(no author information available yet)
Both anti-PD-1 and anti-CTLA4 target subpopulations of exhausted-like CD8(+) T cells.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818953/new-horizons-for-precision-medicine-in-biliary-tract-cancers
#5
REVIEW
Juan W Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X Zhu
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e...
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818952/enasidenib-approved-for-aml-but-best-uses-unclear
#6
(no author information available yet)
The FDA approved the targeted therapy enasidenib for patients with refractory or relapsed acute myeloid leukemia with mutant IDH2 The drug produces remissions in some patients and may reduce the need for blood transfusions, although researchers acknowledge that the FDA's approval came with less supporting evidence than usual.
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28814565/trastuzumab-biosimilar-on-track-for-approval
#7
(no author information available yet)
An FDA expert panel recommended approval of Mylan's MYL-14010, a biosimilar candidate for Genentech's trastuzumab, putting it on track to become the first approved biosimilar for cancer. Experts predict that biosimilars will lead to lower drug prices, but caution that the savings won't be as dramatic as that seen with generics.
August 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28811327/immunotherapy-resistance-genes-identified
#8
(no author information available yet)
A CRISPR-based screen of all 19,050 genes in the genome has revealed around 100 genes that cancer cells must express in order for T cells-and, thus, immunotherapies-to effectively recognize and kill tumors.
August 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28811326/-10m-gift-supports-data-recycling-at-ucsf
#9
(no author information available yet)
The University of California, San Francisco's Institute for Computational Health Sciences has received a $10 million gift to support "data recycling" investigations. The approach to medical research involves mining existing data to potentially uncover new uses for existing drugs and help improve clinical care.
August 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808051/error-prone-dna-repair-targets-the-h3k36me3-chromatin-of-active-genes
#10
(no author information available yet)
Carcinogen-associated error-prone DNA repair increases the mutation rate of active genes in cancer.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808050/inactivating-braf-mutations-modulate-ras-mapk-signaling
#11
(no author information available yet)
Hypoactive BRAF mutants bind more tightly to active RAS and amplify ERK signaling.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808049/the-1q42-1-risk-allele-promotes-melanoma-via-parp1-upregulation
#12
(no author information available yet)
An intronic indel variant enhances RECQL binding to upregulate PARP1 in melanocytic cells.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808048/epigenetic-repression-of-line-1-elements-protects-drug-resistant-cells
#13
(no author information available yet)
H3K9me3-dependent heterochromatin formation maintains drug-tolerant persister (DTP) cell viability.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808047/hr-intermediates-can-induce-chromosomal-translocations
#14
(no author information available yet)
Multi-invasions (MI) are HR intermediates formed when a ssDNA invades two dsDNA.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#15
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28801307/loss-of-mutl-disrupts-chk2-dependent-cell-cycle-control-through-cdk4-6-to-promote-intrinsic-endocrine-therapy-resistance-in-primary-breast-cancer
#16
Svasti Haricharan, Nindo Punturi, Purba Singh, Kimberly R Holloway, Meenakshi Anurag, Jacob Schmelz, Cheryl Schmidt, Jonathan T Lei, Vera Suman, Kelly Hunt, John A Olson, Jeremy Hoog, Shunqiang Li, Shixia Huang, Dean P Edwards, Shyam M Kavuri, Matthew N Bainbridge, Cynthia X Ma, Matthew J Ellis
Significant endocrine therapy-resistant tumor proliferation is present in ≥20% of estrogen receptor positive (ER+) primary breast cancers and is associated with disease recurrence and death. Here, we uncover a link between intrinsic endocrine therapy resistance and dysregulation of the MutL mismatch repair complex (MLH1/3, PMS1/2), and demonstrate a direct role for MutL complex loss in resistance to all classes of endocrine therapy. We find that MutL deficiency in ER+ breast cancer abrogates Chk2-mediated inhibition of CDK4, a prerequisite for endocrine therapy responsiveness...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#17
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28794052/pediatric-match-trial-opens-enrollment
#18
(no author information available yet)
The largest basket study to date of targeted agents in children and adolescents began enrolling patients in late July. Pediatric MATCH will study seven drugs to start; researchers plan to add at least two more in the near future.
August 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28790031/blimp1-induces-transient-metastatic-heterogeneity-in-pancreatic-cancer
#19
Shin-Heng Chiou, Viviana I Risca, Gordon X Wang, Dian Yang, Barbara M Grüner, Arwa S Kathiria, Rosanna K Ma, Dedeepya Vaka, Pauline Chu, Margaret Kozak, Laura Castellini, Edward E Graves, Grace E Kim, Philippe Mourrain, Albert C Koong, Amato J Giaccia, Monte M Winslow
Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite the clinical significance of metastatic spread, our understanding of molecular mechanisms that drive PDAC metastatic ability remains limited. Using a novel genetically engineered mouse model of human PDAC, we uncover a transient subpopulation of cancer cells with exceptionally high metastatic ability. Global gene expression profiling and functional analyses uncovered the transcription factor Blimp1 as a key driver of PDAC metastasis...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28790030/notch-shapes-the-innate-immunophenotype-in-breast-cancer
#20
Qiang Shen, Brenda Cohen, Weiyue Zheng, Ramtin Rahbar, Bernard Martin, Kiichi Murakami, Sara Lamorte, Patrycja Thompson, Hal Berman, Juan Carlos Zúñiga-Pflücker, Pamela S Ohashi, Michael Reedijk
Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment (TME). Here we show that Notch in tumor cells regulates the expression of two powerful pro-inflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAMs). Notch also regulates TGFβ-mediated activation of tumor cells by TAMs, closing a Notch-dependent paracrine signaling loop between these two cell types. We use a novel mouse model in which Notch can be regulated in spontaneous mammary carcinoma to confirm that IL1β and CCL2 production, and macrophage recruitment are Notch-dependent...
August 8, 2017: Cancer Discovery
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