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Cancer Discovery

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https://www.readbyqxmd.com/read/29242215/talazoparib-bests-chemo-for-breast-cancer
#1
(no author information available yet)
Patients with advanced or metastatic HER2-negative breast cancer and germline BRCA1/2 mutations may benefit from talazoparib, according to data from a phase III trial. Compared with chemotherapy, the investigational PARP inhibitor induced some complete responses, prolonged progression-free survival, and improved patients' overall quality of life.
December 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29242214/expressed-gene-fusions-as-frequent-drivers-of-poor-outcomes-in-hormone-receptor-positive-breast-cancer
#2
Karina J Matissek, Maristela L Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas V Saladi, Allison MacLeay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdogen, Unal Egeli, Sehsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St Louis, Nora Horick, Dianne M Finkelstein, Long Phi Le, Aditya Bardia, Paul E Goss, Dennis C Sgroi, A John Iafrate, Leif W Ellisen
We sought to uncover novel genetic drivers of hormone-receptor positive (HR+) breast cancer, employing a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes including PIK3CA, AKT3, RAF1 and ESR1 in 14% (24/173) of unselected patients with advanced HR+ breast cancer. Fluorescence in situ hybridization (FISH) confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors...
December 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29237612/ctcs-may-predict-breast-cancer-recurrence
#3
(no author information available yet)
Findings from a prospective study indicate that for patients diagnosed with ER-positive, HER2-negative breast cancer, the presence of circulating tumor cells several years afterward considerably ups the risk-by nearly 22-fold-of their disease making a late reappearance.
December 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29237611/anti-pd-1-therapy-ok-for-most-with-hiv
#4
(no author information available yet)
The PD-1 inhibitor pembrolizumab poses no significant risks for patients with HIV and cancer, according to data presented at a recent meeting of the Society for Immunotherapy of Cancer. The findings suggest that patients with HIV should no longer be excluded from clinical trials testing checkpoint inhibitors and other novel therapies for cancer.
December 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29233825/rapid-responses-to-avapritinib-blu-285-in-mastocytosis
#5
(no author information available yet)
In a phase I trial of avapritinib (formerly BLU-285), which targets D816V mutant KIT, for the treatment of advanced systemic mastocytosis, patients experienced rapid and durable disease control. The overall response rate was 72%, and 56% of patients experienced a complete or partial response. No patients discontinued treatment due to adverse events, most of which were mild to moderate in nature.
December 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29233824/role-for-immune-therapy-in-advanced-breast-cancer
#6
(no author information available yet)
In a phase Ib/II trial, adding the PD-1 inhibitor pembrolizumab to trastuzumab showed clinical benefit in patients with advanced HER2-positive breast cancer who had developed resistance to trastuzumab. The study also identified tumor-infiltrating lymphocyte levels as a potential biomarker of response to treatment.
December 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29229753/fusobacterium-travels-with-colorectal-cancer-cells
#7
(no author information available yet)
Fusobacterium is enriched in colorectal cancer, but until now it has been unclear whether these bacteria drive tumorigenesis. A recent study shows that colorectal cancer cells take their microbiomes with them as they metastasize-and that targeting Fusobacterium with antibiotics reduces tumor growth in mice xenografts.
December 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29229752/ribociclib-extends-survival-in-hr-breast-cancer
#8
(no author information available yet)
Adding the CDK4/6 inhibitor ribociclib to standard first-line endocrine therapy significantly prolonged survival in premenopausal and perimenopausal women with advanced HR-positive, HER2-negative breast cancer enrolled in the MONALEESA-7 trial. This is the first definitive evidence that CDK4/6 inhibitor-based therapy is effective for first-line treatment of premenopausal and perimenopausal women.
December 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222191/nfs1-expression-protects-lung-tumor-cells-from-ferroptosis
#9
(no author information available yet)
NFS1 activity is essential for maintenance of iron-sulfur cluster biosynthesis in response to oxidative stress.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222190/loss-of-dna-repair-drives-neoantigen-renewal-and-inhibits-tumor-growth
#10
(no author information available yet)
DNA mismatch repair in tumors promotes enhanced immune surveillance.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222189/osteoblasts-promote-release-of-tumor-promoting-siglecfhi-neutrophils
#11
(no author information available yet)
Lung tumors activate OCN+ osteoblasts in distant bone stroma to supply tumor-infiltrating neutrophils.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222188/myc-induces-immune-suppression-to-promote-lung-tumorigenesis
#12
(no author information available yet)
MYC promotes angiogenesis, inflammation, and immune suppression to accelerate KRASG12D tumor growth.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29222187/mutant-idh1r132h-induces-transcriptional-and-epigenomic-reprogramming
#13
(no author information available yet)
A fraction of the chromatin state and DNA methylation changes induced by IDH1R132H are irreversible.
December 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29217691/first-line-osimertinib-beneficial-in-advanced-nsclc
#14
(no author information available yet)
Osimertinib is more effective as first-line therapy than other EGFR inhibitors for patients with advanced EGFR-mutated non-small cell lung cancer-notably Asians, who have a higher incidence of the disease compared with Western populations. The conclusion is based on data from a subgroup analysis of the phase III FLAURA trial.
December 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29208604/jcar015-in-all-a-root-cause-investigation
#15
(no author information available yet)
After conducting an internal probe of the five deaths that halted JCAR015's development for acute lymphoblastic leukemia, Juno Therapeutics has concluded that multiple factors were at play. A surge in inflammatory cytokine levels from rapid, early T-cell proliferation may have provoked the blood-brain barrier disruption seen in these patients, inducing fatal cerebral edema.
December 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29203461/identifying-and-targeting-sporadic-oncogenic-genetic-aberrations-in-mouse-models-of-triple-negative-breast-cancer
#16
Hui Liu, Charles J Murphy, Florian A Karreth, Kristina B Emdal, Forest M White, Olivier Elemento, Alex Toker, Gerburg M Wulf, Lewis C Cantley
Triple negative breast cancers (TNBC) are genetically characterized by aberrations in TP53 and a low rate of activating point mutations in common oncogenes, rendering it challenging in applying targeted therapies. We performed whole exome sequencing (WES) and RNAseq to identify somatic genetic alterations in mouse models of TNBCs driven by loss of Trp53 alone or in combination with Brca1. Amplifications or translocations that resulted in elevated oncoprotein expressions or oncoprotein-containing fusions, respectively, as well as frame-shift mutations of tumor suppressors were identified in approximately 50% of the tumors evaluated...
December 4, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29196469/pancreatitis-induced-p62-accumulation-promotes-pancreatic-cancer
#17
(no author information available yet)
Defective autophagy and stress in acinar cells drives the progression of PanIN1 lesions to PDAC.
December 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29196468/cdk4-6-inhibitors-increase-pd-l1-expression
#18
(no author information available yet)
Cyclin D/CDK4 destabilize PD-L1 via the CUL3SPOP E3 ligase to increase tumor-infiltrating lymphocytes.
December 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29196467/atr-promotes-faithful-chromosome-segregation-in-mitosis
#19
(no author information available yet)
ATR localized to centromeres to prevent lagging chromosomes independent of its role in replication stress.
December 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29196466/pmn-mdsc-infiltration-blocks-the-antitumor-effects-of-csf1r-inhibition
#20
(no author information available yet)
CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.
December 1, 2017: Cancer Discovery
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