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Cancer Discovery

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https://www.readbyqxmd.com/read/27903500/primary-resistance-to-pd-1-blockade-mediated-by-jak%C3%A2-mutations
#1
Daniel Sanghoon Shin, Jesse M Zaretsky, Helena Escuin-Ordinas, Angel Garcia-Diaz, Siwen Hu-Lieskovan, Anusha Kalbasi, Catherine S Grasso, Willy Hugo, Salemiz Sandoval, Davis Y Torrejon, Nicolaos Palaskas, Gabriel Abril Rodriguez, Giulia Parisi, Ariel Azhdam, Bartosz Chmielowski, Grace Cherry, Elizabeth Seja, Beata Berent-Maoz, I Peter Shintaku, Dung Thi Le, Drew M Pardoll, Luis A Diaz, Paul C Tumeh, Thomas G Graeber, Roger S Lo, Begoña Comin-Anduix, Antoni Ribas
Loss of function mutations in JAK½ can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned they may also be involved in primary resistance to anti-PD-1 therapy. JAK½ inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK½ mutations, which led to lack of PD-L1 expression upon interferon gamma exposure mediated by inability to signal through the interferon gamma receptor pathway...
November 30, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27899405/brigatinib-effective-in-alk-nsclc
#2
(no author information available yet)
Results from a phase I/II trial indicate that the investigational ALK inhibitor brigatinib is active in patients with ALK-rearranged non-small cell lung cancer. Patients who had previously received crizotinib-as well as those who hadn't-responded to the drug, which was also active in patients with brain metastases.
November 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27899404/tapping-big-data-to-help-little-patients
#3
(no author information available yet)
Through a large-scale tumor-sequencing effort for pediatric brain cancer, researchers hope to bring personalized care to young patients.
November 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27881455/egfr-undergoes-ligand-induced-conformational-changes-during-activation
#4
(no author information available yet)
Ligand binding reduces the conformational entropy of the EGFR ECD to promote EGFR dimerization.
November 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27881454/cabozantinib-is-active-in-patients-with-advanced-ret-rearranged-nsclc
#5
(no author information available yet)
Cabozantinib achieved an overall response rate of 28% in patients with RET-rearranged NSCLC.
November 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27881453/cabozantinib-is-more-effective-than-erlotinib-in-egfr-wild-type-nsclc
#6
(no author information available yet)
Cabozantinib alone or in combination with erlotinib extended survival compared with erlotinib alone.
November 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27881452/arginine-methylation-of-mdh1-disrupts-pdac-metabolism-and-growth
#7
(no author information available yet)
Hypomethylation of MDH1 enhances glutamine metabolism and cellular proliferation in PDAC.
November 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27872130/a-first-in-human-phase-i-study-of-the-atp-competitive-akt-inhibitor-ipatasertib-gdc-0068-demonstrates-robust-and-safe-targeting-of-akt-in-patients-with-solid-tumors
#8
Cristina Saura, Desamparados Roda, Susana Roselló, Mafalda Oliveira, Teresa Macarulla, José Alejandro Pérez-Fidalgo, Rafael Morales-Barrera, Juan Manuel Sanchis-García, Luna Musib, Nageshwar Budha, Jin Zhu, Michelle Nannini, Wai Y Chan, Sandra M Sanabria Bohórquez, Raymond D Meng, Kui Lin, Yibing Yan, Premal Patel, José Baselga, Josep Tabernero, Andres Cervantes
Activation of Akt signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers but targeting Akt has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of Akt. Ipatasertib (GDC‑0068) is a novel selective ATP-competitive small molecule inhibitor of Akt that preferentially targets active phosphorylated Akt and is potent in cell lines with evidence of Akt activation. In this Phase I study, ipatasertib was well-tolerated; most adverse events were gastrointestinal and Grade 1-2 in severity...
November 21, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27872129/carcinogens-report-lists-seven-new-substances
#9
(no author information available yet)
The National Toxicology Program has added seven new substances to its 14th Report on Carcinogens, bringing the total number in this congressionally mandated report to 248. The latest additions are the chemical trichloroethylene; cobalt metal and compounds that release cobalt ions in vivo; and five viruses, including HIV-1.
November 21, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27872128/correction-molecular-heterogeneity-and-receptor-coamplification-drive-resistance-to-targeted-therapy-in-met-amplified-esophagogastric-cancer
#10
(no author information available yet)
No abstract text is available yet for this article.
November 21, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27872127/targeting-cancer-metabolism-dietary-and-pharmacologic-interventions
#11
REVIEW
Claudio Vernieri, Stefano Casola, Marco Foiani, Filippo Pietrantonio, Filippo de Braud, Valter Longo
: Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies...
November 21, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864232/bringing-precision-medicine-to-community-oncologists
#12
(no author information available yet)
Quest Diagnostics has teamed up with Memorial Sloan Kettering Cancer Center and IBM Watson Health to offer IBM Watson Genomics to its network of community cancer centers and hospitals. This new service aims to advance precision medicine by combining genomic tumor sequencing with the power of cognitive computing.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864231/pi3k%C3%AE-inhibition-potentiates-immune-checkpoint-blockade
#13
(no author information available yet)
Targeting PI3Kγ overcomes myeloid cell-mediated resistance to immune checkpoint blockade.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864230/the-circadian-clock-protein-cry2-promotes-myc-degradation
#14
(no author information available yet)
CRY2 recruits SCF(FBXL3) to ubiquitinate MYC, promoting MYC degradation and preventing transformation.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864229/an-antibody-mimetic-screen-identifies-a-targetable-ras-allosteric-site
#15
(no author information available yet)
Monobodies specific for the dimerization interface of RAS inhibit RAS activation and signaling.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864228/ifn%C3%AE-mutations-prompt-ctla-4-inhibitor-resistance
#16
(no author information available yet)
A recent study pinpoints loss of IFNγ signaling as one reason why many patients do not respond to the CTLA-4 inhibitor ipilimumab. Analyzing whole-exome tumor sequencing data from 16 patients with melanoma, the researchers found multiple copy-number alterations that led to the loss of key IFNγ pathway genes in 12 ipilimumab nonresponders. Mice bearing melanoma tumors that lacked one of these genes, IFNGR1, also had an impaired response to anti-CTLA-4 therapy and significantly reduced overall survival, compared with their counterparts whose tumors had intact IFNGR1...
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864227/fmn2-generates-a-prometastatic-perinuclear-actin-structure
#17
(no author information available yet)
FMN2 prevents DNA damage and cell death during migration by establishing a perinuclear actin structure.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27864226/pinpointing-cancer-stem-cells-in-oligodendroglioma
#18
(no author information available yet)
Through single-cell RNA sequencing of low-grade oligodendrogliomas, researchers have identified a cell population featuring a gene expression signature similar to those of neural stem and progenitor cells. These cancer stem cells have enriched proliferative potential and may be responsible for fueling the growth of this glioma subtype.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27852627/co-opting-innate-and-adaptive-immunity-against-cancer
#19
(no author information available yet)
Researchers at the Massachusetts Institute of Technology in Cambridge have devised a way to completely eradicate large, established tumors in mice. Their four-component strategy comprises a tumor-specific antibody and vaccine, along with IL2 and anti-PD-1 therapy, which employs both innate and adaptive immunity for tumor destruction.
November 16, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27836892/a-microenvironment-screen-identifies-compounds-targeting-pre-lscs
#20
(no author information available yet)
2-ME2 selectively targets pre-LSCs by inhibiting MYC translation and SCL activity.
November 11, 2016: Cancer Discovery
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