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Cancer Discovery

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https://www.readbyqxmd.com/read/30104334/improved-survival-seen-for-some-with-pancreatic-cancer
#1
(no author information available yet)
In two pancreatic cancer trials-the randomized phase III PRODIGE 24/CCTG PA.6 and PREOPANC-1 trials-researchers found that experimental drug regimens for patients with resectable adenocarcinomas increased overall survival or showed a trend in that direction. The findings could prompt changes in clinical practice for these patients.
August 13, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30104333/a-digital-rna-signature-of-circulating-tumor-cells-predicting-early-therapeutic-response-in-localized-and-metastatic-breast-cancer
#2
Tanya T Kwan, Aditya Bardia, Laura M Spring, Anita Giobbie-Hurder, Mark Kalinich, Taronish Dubash, Tilak Sundaresan, Xin Hong, Joseph A LiCausi, Uyen Ho, Erin J Silva, Ben S Wittner, Lecia V Sequist, Ravi Kapur, David T Miyamoto, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)-derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC-Score after three cycles of neoadjuvant therapy is associated with residual disease at surgery (p=0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC-Score correlates with overall survival (p= 0...
August 13, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30097427/a-kat6a-b-inhibitor-induces-senescence-to-suppress-tumorigenesis
#3
(no author information available yet)
The reversible competitive KAT6A/B inhibitor WM-1119 enhanced oncogene-induced senescence.
August 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30097426/akt1-can-be-activated-via-distinct-phosphorylation-based-mechanisms
#4
(no author information available yet)
Phosphorylation of Ser473 and dual phosphorylation of Ser477/Thr479 activate AKT via distinct mechanisms.
August 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30097425/erg-retargets-baf-complexes-to-promote-prostate-oncogenesis
#5
(no author information available yet)
In TMPRSS2-ERG -positive prostate cancer, ERG retargets BAF chromatin remodeling complexes to ETS motifs.
August 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30097424/glioblastoma-arises-from-cells-in-the-subventricular-zone
#6
(no author information available yet)
Low-level driver mutations in subventricular zone (SVZ) cells are sufficient to induce glioblastoma.
August 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30093506/the-btk-inhibitor-arq-531-targets-ibrutinib-resistant-cll-and-richter-s-transformation
#7
Sean David Reiff, Rose Mantel, Lisa L Smith, Joseph T Greene, Elizabeth M Muhowski, Catherine A Fabian, Virginia M Goettl, Minh Tran, Bonnie Harrington, Kerry A Rogers, Farrukh T Awan, Kami Maddocks, Leslie Andritsos, Amy M Lehman, Deepa Sampath, Rosa Lapalombella, Sudharshan Eathiraj, Giovanni Abbadessa, Brian Schwartz, Amy Johnson, John C Byrd, Jennifer A Woyach
Targeted inhibition of Bruton's tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL). Here we describe preclinical investigations of ARQ 531, a potent, reversible inhibitor of BTK with additional activity against Src family kinases and kinases related to ERK signaling. We hypothesized that targeting additional kinases would improve global inhibition of signaling pathways, producing more robust responses...
August 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30093505/ivosidenib-gets-go-ahead-for-aml
#8
(no author information available yet)
The FDA approved ivosidenib for patients with IDH1 -mutant relapsed/refractory acute myeloid leukemia. The approval was based on results of a phase I trial in which 32.8% of patients treated with the drug had a complete remission or a complete remission with a partial hematologic recovery.
August 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30093504/crispr-causes-unexpected-genomic-damage
#9
(no author information available yet)
A study in four cell lines concludes that CRISPR/Cas9 editing causes unanticipated genomic alterations, including large deletions, translocations, and insertions. Some of these changes could be the first hits that cause cells to eventually become neoplastic.
August 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30093503/repotrectinib-tpx-0005-is-a-next-generation-ros1-trk-alk-inhibitor-that-potently-inhibits-ros1-trk-alk-solvent-front-mutations
#10
Alexander Drilon, Sai-Hong I Ou, Byoung Chul Cho, Dong-Wan Kim, Jeeyun Lee, Jessica J Lin, Viola W Zhu, Myung-Ju Ahn, D Ross Camidge, Judy Nguyen, Dayong Zhai, Wei Deng, Zhongdong Huang, Evan Rogers, Juliet Liu, Jeff Whitten, John K Lim, Shanna Stopatschinskaja, David M Hyman, Robert C Doebele, J Jean Cui, Alice T Shaw
The use of tyrosine kinase inhibitors (TKIs) with activity against ALK, ROS1, or TRKA-C can result in significant clinical benefit in patients with diverse tumors harboring ALK, ROS1 or NTRK1-3 rearrangements; however, resistance invariably develops. The emergence of on-target kinase domain mutations represents a major mechanism of acquired resistance. Solvent front substitutions such as ALK G1202R, ROS1 G2032R or D2033N, TRKA G595R, and TRKC G623R are among the most recalcitrant of these mechanisms. Repotrectinib (TPX-0005) is a rationally-designed, low molecular weight, macrocyclic TKI that is selective and highly potent against ROS1, TRKA-C, and ALK...
August 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30087097/mhc-expression-predicts-checkpoint-blockade-response
#11
(no author information available yet)
MHC expression may affect response to immune checkpoint inhibitors in patients with advanced melanoma. In a recent retrospective analysis, patients with low MHC class I expression responded to a PD-1 inhibitor, but were less likely to respond to a CTLA4 inhibitor than patients with higher MHC class I expression.
August 7, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30076152/lysine-methyltransferase-and-demethylases-regulate-dna-amplifications
#12
(no author information available yet)
Transient site-specific DNA copy-number gains (TSSG) are controlled by histone lysine methylation dynamics.
August 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30076151/ifn-driven-endogenous-retroviruses-can-drive-tumor-innate-immunity
#13
(no author information available yet)
IFN-inducible endogenous retroviruses promote mesenchymal tumor cell-mediated immunosuppression.
August 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30076150/advice-offered-for-sharing-research-results
#14
(no author information available yet)
A report from the National Academies of Sciences, Engineering, and Medicine lays out 12 recommendations to help scientists decide whether to return research results to study participants and, if they do, how to improve the sharing of information. The most important change the report recommends is harmonizing contradictory regulations on data sharing.
August 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30076149/dub3-deubiquitinates-brd4-to-promote-prostate-cancer-progression
#15
(no author information available yet)
DUB3-mediated BRD4 stabilization overcomes SPOP-mediated degradation to confer BET inhibitor resistance.
August 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30076148/notch1-signaling-hijacks-the-stress-response-to-promote-t-all
#16
(no author information available yet)
The heat shock transcription factor HSF1 is upregulated in patients with T-ALL.
August 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30072408/small-cell-prostate-cancer-variety-surprisingly-common
#17
(no author information available yet)
A recent study finds that treatment-emergent small-cell neuroendocrine prostate cancer occurs in 17% of patients with the metastatic, castration-resistant form of the disease. This small-cell variety of prostate cancer shows a distinct gene expression signature and reduces patients' survival by nearly 20%.
August 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30068509/understanding-prostate-cancer-in-african-american-men
#18
(no author information available yet)
The NIH has launched a large-scale, prospective study on prostate cancer in African-American men. The study will integrate genomic data with information on lifestyle and social risk factors to investigate why African-American men are more likely to develop aggressive disease than white men.
August 1, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30054289/zhx2-is-an-oncogenic-driver-of-kidney-cancer
#19
(no author information available yet)
Loss of VHL-mediated degradation of ZHX2 promotes clear cell renal cell carcinoma growth.
July 27, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30054288/hpv-testing-bests-pap-for-cervical-screening
#20
(no author information available yet)
Primary human papillomavirus (HPV) testing may be better than Pap testing at screening for cervical cancer: In the HPV FOCAL study, HPV testing detected precancerous cervical lesions earlier than Pap testing, and it was less likely to miss early signs of disease.
July 27, 2018: Cancer Discovery
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