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Cancer Discovery

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https://www.readbyqxmd.com/read/28314722/complement-component-3-promotes-leptomeningeal-metastasis
#1
(no author information available yet)
Cancer cell-derived C3 is essential for the growth of disseminated cancer cells in the CSF.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28314721/t-cell-bispecific-antibodies-suppress-multiple-myeloma
#2
(no author information available yet)
T-cell bispecific antibodies (TCB) targeting BCMA or FcRH5 induce T cell-mediated myeloma cell death.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28314720/rechallenge-with-braf-and-mek-inhibitors-has-antitumor-activity
#3
(no author information available yet)
Resistance to BRAF plus MEK inhibitors may be reversible in patients with BRAF(V600)-mutant melanoma.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28314719/targeting-class-iia-hdacs-may-suppress-breast-tumors-and-metastases
#4
(no author information available yet)
Inhibition of class IIa HDACs with TMP195 promotes a macrophage-dependent reduction in tumor burden.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28302600/irecist-guideline-unveiled-for-immunotherapies
#5
(no author information available yet)
The new iRECIST guideline-developed in consultation with academics, drug companies, and regulatory authorities-provides a standardized approach to assessing whether patients' disease improves, stays the same, or worsens in trials of immunotherapeutics, agents that can trigger different response patterns from other kinds of drugs.
March 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28302599/a-different-path-for-harnessing-trail
#6
(no author information available yet)
Two studies show that the apoptosis-inducing protein TRAIL also induces release of cytokines that promote tumor growth. TRAIL triggers formation of a signaling complex that activates NF-κB. Loss of one component of the signaling complex, the adaptor protein FADD, reduces the number of lung tumors in mice.
March 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28288994/immunotherapy-beats-chemo-for-bladder-cancer
#7
(no author information available yet)
Patients with advanced urothelial carcinoma live 3 months longer, on average, when given pembrolizumab as a second-line treatment instead of chemotherapy. The finding is based on data from the first phase III trial to test an immunotherapeutic in these patients, which could lead to another label indication for the PD-1 inhibitor.
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28288993/a-combined-pd-1-c5a-blockade-synergistically-protects-against-lung-cancer-growth-and-metastasis
#8
Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, Maria J Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J Lasarte, Silvestre Vicent, Axel Vater, Fernando Lecanda, Luis M Montuenga, Ruben Pio
Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that a combined inhibition of C5a/C5aR1 and PD-1 signaling may have an antitumor synergistic effect. RMP1-14 antibody was used to block PD-1 and an L-aptamer to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer we demonstrate that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis, and leads to prolonged survival...
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28288992/identification-of-a-dna-damage-induced-alternative-splicing-pathway-that-regulates-p53-and-cellular-senescence-markers
#9
Jing Chen, John Crutchley, Dadong Zhang, Kouros Owzar, Michael B Kastan
Cellular responses to DNA damage are critical determinants of cancer development and aging-associated pathogenesis. Here we report a novel DNA damage response pathway that regulates alternative splicing of numerous gene products, including the human tumor suppressor p53, and controls DNA damage-induced cellular senescence. In brief, ionizing irradiation (IR) inhibits the activity of hSMG-1, a phosphoinositide-3-kinase-like kinase (PIKK) family member, reducing the binding of hSMG1 to a specific region of p53 precursor mRNA near exon 9 and promoting the binding of ribosomal protein L26 (RPL26) to p53 pre-mRNA...
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28283507/inhibition-of-ezh2-or-bet-suppresses-diffuse-intrinsic-pontine-glioma
#10
(no author information available yet)
H3K27M-expressing diffuse intrinsic pontine gliomas (DIPG) are dependent on residual PRC2 activity.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28283506/enl-is-an-essential-acetyl-histone-reader-in-acute-myeloid-leukemia
#11
(no author information available yet)
ENL binds acetylated histone 3 to promote oncogenic gene expression and AML cell proliferation.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28283505/the-bipartite-substrate-binding-site-in-mrp1-recognizes-diverse-structures
#12
(no author information available yet)
The substrate binding site in MRP1 contains a positively charged region and a hydrophobic region.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28283504/mk-8242-is-active-in-patients-with-p53-wild-type-advanced-solid-tumors
#13
(no author information available yet)
The MDM2 inhibitor MK-8242 is tolerable in patients with liposarcoma and other advanced solid tumors.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28283503/her2-tumor-molecular-subtypes-predict-response-to-dual-her2-blockade
#14
(no author information available yet)
Trastuzumab plus lapatinib achieves the highest response rates in HER2-enriched HER2(+) breast tumors.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28274958/cabozantinib-eradicates-advanced-murine-prostate-cancer-by-activating-anti-tumor-innate-immunity
#15
Akash Patnaik, Kenneth D Swanson, Eva Csizmadia, Aniruddh Solanki, Natalie Landon-Brace, Marina P Gehring, Katja Helenius, Brian M Olson, Athalia R Pyzer, Lily C Wang, Olivier Elemento, Jesse Novak, Thomas B Thornley, John M Asara, Laleh Montaser, Joshua J Timmons, Todd M Morgan, Yugang Wang, Elena Levantini, John G Clohessy, Kathleen Kelly, Pier Paolo Pandolfi, Jacalyn M Rosenblatt, David E Avigan, Huihui Ye, Jeffrey M Karp, Sabina Signoretti, Steven P Balk, Lewis C Cantley
Several kinase inhibitors that target aberrant signaling pathways in tumor cells have been deployed in cancer therapy. However, their impact on the tumor immune microenvironment remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed striking responses in cancer clinical trial patients across several malignancies. Here we show that cabozantinib rapidly eradicates invasive, poorly-differentiated PTEN/p53 deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor...
March 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28274957/an-acquired-her2-t798i-gatekeeper-mutation-induces-resistance-to-neratinib-in-a-patient-with-her2-mutant-driven-breast-cancer
#16
Ariella B Hanker, Monica Red Brewer, Jonathan H Sheehan, James P Koch, Gregory R Sliwoski, Rebecca Nagy, Richard Lanman, Michael F Berger, David M Hyman, David B Solit, Jie He, Vincent Miller, Richard E Cutler, Alshad S Lalani, Darren Cross, Christine M Lovly, Jens Meiler, Carlos L Arteaga
We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding...
March 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28270385/revised-common-rule-allows-broad-consent
#17
(no author information available yet)
The U.S. Department of Health and Human Services has revised the Common Rule governing the protection of patients who donate biospecimens for research. The final rule eliminates a controversial proposal that would have required researchers to obtain renewed consent for use of donated samples beyond their original purpose.
March 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28258104/tumor-endothelial-notch-signaling-drives-metastasis-via-vcam1
#18
(no author information available yet)
Tumor cell-induced endothelial cell Notch1 signaling promotes neutrophil infiltration and metastasis.
March 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28258103/protecting-pten-in-the-nucleus
#19
(no author information available yet)
A recent study shows that the transport receptor Importin-11 relocates PTEN, a tumor suppressor, to the nucleus, preventing its degradation in the cytoplasm. Mice lacking Importin-11 are prone to lung cancers, and its absence in human prostate and lung tumors signals a poorer prognosis.
March 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28258102/whole-genome-sequencing-defines-the-mutational-landscape-of-pannets
#20
(no author information available yet)
PanNET mutations affect DNA damage repair, chromatin remodeling, telomere maintenance, and mTOR signaling.
March 3, 2017: Cancer Discovery
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