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Cancer Discovery

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https://read.qxmd.com/read/30877087/nad-kinase-is-an-akt-substrate
#1
(no author information available yet)
AKT-mediated phosphorylation of NAD kinase induces synthesis of NADP+ and NADPH.
March 15, 2019: Cancer Discovery
https://read.qxmd.com/read/30877086/inhibition-of-qpctl-induces-myeloid-immune-checkpoint-blockade
#2
(no author information available yet)
Glutaminyl-peptide cyclotransferase-like (QPCTL) is a modifier of the CD47-SIRPα myeloid checkpoint.
March 15, 2019: Cancer Discovery
https://read.qxmd.com/read/30877085/patient-driven-discovery-therapeutic-targeting-and-post-clinical-validation-of-a-novel-akt1-fusion-driven-cancer
#3
Emily K Slotkin, Daniel Diolaiti, Neerav N Shukla, Filemon S Dela Cruz, Jennifer J Clark, Gunes Gundem, Venkata D Yellapantula, Max F Levine, Daoqi You, Peilin Ma, Sagarika Pachhal, Glorymar Ibanez Sanchez, Ryma Benayed, Achim A Jungbluth, Lillian M Smyth, Audrey Mauguen, Irena Gushterova, Hongxu Ding, Lee Spraggon, Robert Darnell, Andrea Califano, Marc Ladanyi, Elli Papaemmanuil, Andrew L Kung, David M Hyman, Stephen S Roberts
Despite the important role of the PI3K/AKT/mTOR axis in the pathogenesis of cancer, to date there have been few functional oncogenic fusions identified involving the AKT genes. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion between the LAMTOR1 and AKT1 genes. Through expanded use access, she became the first pediatric patient to be treated with the oral ATP-competitive pan-AKT inhibitor ipatasertib. Treatment resulted in dramatic tumor regression demonstrating through patient-driven discovery that the fusion resulted in activation of AKT1, was an oncogenic driver, and could be therapeutically targeted with clinical benefit...
March 15, 2019: Cancer Discovery
https://read.qxmd.com/read/30877084/hepatocyte-signaling-mediates-a-prometastatic-niche-in-the-liver
#4
(no author information available yet)
Hepatocyte-mediated inflammatory signaling is critical for liver metastasis.
March 15, 2019: Cancer Discovery
https://read.qxmd.com/read/30877083/potentially-actionable-map3k8-alterations-are-common-in-spitzoid-melanoma
#5
(no author information available yet)
Fusions or truncations of MAP3K8 occur in 33% of spitzoid melanomas and 1.5% of adult melanomas.
March 15, 2019: Cancer Discovery
https://read.qxmd.com/read/30872263/eyeing-enzalutamide-for-hormone-sensitive-prostate-cancer
#6
(no author information available yet)
In men with metastatic hormone-sensitive prostate cancer, the androgen-receptor inhibitor enzalutamide prolonged radiographic progression-free survival more than a placebo did when given with androgen-deprivation therapy.
March 14, 2019: Cancer Discovery
https://read.qxmd.com/read/30867161/challenges-for-the-clinical-development-of-pi3k-inhibitors-strategies-to-improve-their-impact-in-solid-tumors
#7
REVIEW
Ariella B Hanker, Virginia Kaklamani, Carlos L Arteaga
The PI3K pathway is mutated and aberrantly activated in many cancers and plays a central role in tumor cell proliferation and survival, making it a rational therapeutic target. Until recently, however, results from clinical trials with PI3K inhibitors in solid tumors have been largely disappointing. Here, we describe several factors that have limited the success of these agents, including the weak driver oncogenic activity of mutant PI3K, suboptimal patient selection in trials, drug-related toxicities, feedback upregulation of compensatory mechanisms when PI3K is blocked, increased insulin production upon PI3Kα inhibition, lack of mutant-specific inhibitors, and a relative scarcity of studies using combinations with PI3K antagonists...
March 13, 2019: Cancer Discovery
https://read.qxmd.com/read/30867160/adc-could-benefit-some-with-breast-cancer
#8
(no author information available yet)
Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A phase III trial is under way to compare its safety and efficacy with that of standard chemotherapy.
March 13, 2019: Cancer Discovery
https://read.qxmd.com/read/30862724/mutant-and-wild-type-isocitrate-dehydrogenase-1-share-enhancing-mechanisms-involving-distinct-tyrosine-kinase-cascades-in-cancer
#9
Dong Chen, Siyuan Xia, Mei Wang, Ruiting Lin, Yuancheng Li, Hui Mao, Mike Aguiar, Christopher A Famulare, Alan H Shih, Cameron W Brennan, Xue Gao, Yaozhu Pan, Shuangping Liu, Jun Fan, Lingtao Jin, Lina Song, An Zhou, Joydeep Mukherjee, Russell O Pieper, Ashutosh Mishra, Junmin Peng, Martha Arellano, William G Blum, Sagar Lonial, Titus J Boggon, Ross L Levine, Jing Chen
Isocitrate dehydrogenase 1 (IDH1) is important for reductive carboxylation in cancer cells, and IDH1 R132H mutant plays a pathogenic role in cancers including acute myeloid leukemia (AML). However, the regulatory mechanisms modulating IDH1 mutant and/or wild-type (WT) function remain unknown. Here we show that two groups of tyrosine kinases (TKs) enhance the activation of IDH1 mutant and WT through preferential Y42 or Y391 phosphorylation. Mechanistically, Y42 phosphorylation occurs in IDH1 monomers, which promotes dimer formation with enhanced substrate (isocitrate or a-ketoglutarate) binding, while Y42-phosphorylated dimers show attenuated disruption to monomers...
March 12, 2019: Cancer Discovery
https://read.qxmd.com/read/30862723/cancer-vaccines-steering-t-cells-down-the-right-path-to-eradicate-tumors
#10
Patrick A Ott, Catherine J Wu
<b/> Lack of tumor T-cell infiltration is a barrier to the efficacy of immune checkpoint inhibitors and other immunotherapies in patients with cancer. Because of their ability to activate and augment tumor-specific T cells, vaccines are an attractive approach to direct T-cell responses into the tumor.
March 12, 2019: Cancer Discovery
https://read.qxmd.com/read/30850371/pyruvate-mediates-ecm-remodeling-in-the-lung-metastatic-niche
#11
(no author information available yet)
Pyruvate drives collagen hydroxylation in the extracellular matrix to support breast cancer metastasis.
March 8, 2019: Cancer Discovery
https://read.qxmd.com/read/30850370/engineered-t-cells-bypass-death-signaling-and-bolster-immunotherapy
#12
(no author information available yet)
Disruption of FasL-induced apoptosis of adoptively transferred T cells enhances antitumor efficacy.
March 8, 2019: Cancer Discovery
https://read.qxmd.com/read/30850369/macrophage-derived-nucleosides-reduce-the-efficacy-of-gemcitabine
#13
(no author information available yet)
Pancreatic cancer cells alternatively activate macrophages to release pyrimidines.
March 8, 2019: Cancer Discovery
https://read.qxmd.com/read/30850368/parsaclisib-has-activity-in-patients-with-b-cell-malignancies
#14
(no author information available yet)
A next-generation PI3Kδ inhibitor achieved objective responses and long-term tolerability in NHL.
March 8, 2019: Cancer Discovery
https://read.qxmd.com/read/30837243/a-stromal-lysolipid-autotaxin-signaling-axis-promotes-pancreatic-tumor-progression
#15
Francesca R Auciello, Vinay Bulusu, Chet Oon, Jacqueline Tait-Mulder, Mark Berry, Sohinee Bhattacharyya, Sergey Tumanov, Brittany L Allen-Petersen, Jason Link, Nicholas D Kendsersky, Esmee Vringer, Michelle Schug, David Novo, Rosa F Hwang, Ronald M Evans, Colin Nixon, Craig Dorrell, Jennifer P Morton, Jim C Norman, Rosalie C Sears, Jurre J Kamphorst, Mara H Sherman
Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features trans-differentiation of tissue-resident pancreatic stellate cells (PSCs) into activated cancer-associated fibroblasts (CAFs), a process induced by PDAC cells but of unclear significance for PDAC progression. Here we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state...
March 5, 2019: Cancer Discovery
https://read.qxmd.com/read/30833376/liquid-biopsy-holds-its-own-in-nsclc
#16
(no author information available yet)
According to the prospective NILE study, cell-free DNA analyses are at least as good as tissue-based genotyping for identifying therapeutically actionable genomic alterations in patients with non-small cell lung cancer; the turnaround time is also significantly shorter.
March 4, 2019: Cancer Discovery
https://read.qxmd.com/read/30824429/aml-is-dependent-on-an-rna-binding-protein-network
#17
(no author information available yet)
A network of RNA-binding proteins maintains splicing and survival in AML.
March 1, 2019: Cancer Discovery
https://read.qxmd.com/read/30824428/darolutamide-slows-metastasis-in-prostate-cancer
#18
(no author information available yet)
The phase III ARAMIS study shows that the androgen-receptor antagonist darolutamide delays metastasis in men with castration-resistant prostate cancer by a median of 22 months compared with a placebo. Researchers also found that side effects associated with other drugs in this class were no more common in the placebo group than the darolutamide group.
March 1, 2019: Cancer Discovery
https://read.qxmd.com/read/30824427/niraparib-shrinks-brca-mutated-prostate-tumors
#19
(no author information available yet)
Niraparib showed promising signs of efficacy in the phase II GALAHAD trial of men with advanced prostate cancer whose tumors harbor mutations in the DNA damage-response pathway, especially among patients with gene defects in BRCA1 or BRCA2 .
March 1, 2019: Cancer Discovery
https://read.qxmd.com/read/30824426/snrnas-exist-as-different-methyl-isoforms-and-are-targets-of-fto
#20
(no author information available yet)
Reversible methylation of spliceosome snRNAs is controlled by the RNA demethylase FTO.
March 1, 2019: Cancer Discovery
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