PARPi focus the spotlight on replication fork protection in cancer

Nature Cell Biology 19, 1309 (2017). doi:10.1038/ncb3638 Author: Katharina Schlacher PARP inhibitors (PARPi) kill BRCA1/2-mutated cancers, which become resistant when DNA repair functions are restored. Now, MUS81 nuclease inhibition due to EZH2 downregulation is found to restore DNA replication fork protection but not repair, leading to PARPi-resistance in mutant BRCA2 cells and patients. This challenges the DNA repair dominance in synthetic lethality.
Source: Nature Cell Biology - Category: Cytology Authors: Tags: News and Views Source Type: research

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Publication date: Available online 19 July 2018Source: CellAuthor(s): Max A. Horlbeck, Albert Xu, Min Wang, Neal K. Bennett, Chong Y. Park, Derek Bogdanoff, Britt Adamson, Eric D. Chow, Martin Kampmann, Tim R. Peterson, Ken Nakamura, Michael A. Fischbach, Jonathan S. Weissman, Luke A. GilbertSummarySeminal yeast studies have established the value of comprehensively mapping genetic interactions (GIs) for inferring gene function. Efforts in human cells using focused gene sets underscore the utility of this approach, but the feasibility of generating large-scale, diverse human GI maps remains unresolved. We developed a CRISPR...
Source: Cell - Category: Cytology Source Type: research
Publication date: Available online 19 July 2018Source: CellAuthor(s): David A. Quigley, Ha X. Dang, Shuang G. Zhao, Paul Lloyd, Rahul Aggarwal, Joshi J. Alumkal, Adam Foye, Vishal Kothari, Marc D. Perry, Adina M. Bailey, Denise Playdle, Travis J. Barnard, Li Zhang, Jin Zhang, Jack F. Youngren, Marcin P. Cieslik, Abhijit Parolia, Tomasz M. Beer, George Thomas, Kim N. ChiSummaryWhile mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resista...
Source: Cell - Category: Cytology Source Type: research
I made the pilgrimage to storied Manhattan last week for the first conference organized by the Life Extension Advocacy Foundation (LEAF), titled Ending Age-Related Diseases. It was well organized, all in all a very professional effort. Congratulations are due to the volunteers who set it all up and kept everything moving smoothly. The attendees were a mix of researchers, entrepreneurs, advocates, interested members of the public, and investors of various stripes - a good mix, one that in the present excitable market environment provoked a great deal of useful networking. The presentations were recorded and will star...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Authors: Jin Z, Xu L, Zhang L, Zhao M, Li D, Ye L, Ma Y, Ren S, Yu H, Wang D, Liang C, Chen B Abstract Interleukin enhancer binding factor 2 (ILF2) participates in several aspects of DNA and RNA metabolism and regulates gene expression at multiple levels; however, its role in breast cancer remains undefined. The variant statuses of ILF2 in human breast cancer were evaluated using the COSMIC database. Altered ILF2 expression in normal breast tissue relative to cancer tissue and in breast cancer patients with different clinicopathological characteristics, molecular subtypes, clinical outcomes and chemotherapy respons...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-EGFR and anti-VEGF agents, the relevance of primary tumour location and novel subgroups such as BRAF mutated, HER2 amplified and mismatch-repair deficient cancers. Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for mCRC. The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumo...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Contributors : Max A Horlbeck ; Jonathan S Weissman ; Luke A GilbertSeries Type : OtherOrganism : Homo sapiensSeminal yeast studies have established the value of comprehensively mapping genetic interactions (GIs) for inferring gene function. Efforts in human cells using focused gene sets underscore the utility of this approach, but the feasibility of generating large-scale, diverse human GI maps remains unresolved. We developed a CRISPR interference platform for large-scale quantitative mapping of human GIs. We systematically perturbed 222,784 gene pairs in two cancer cell lines. The resultant maps cluster functionally rel...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
While studying two rare inherited cancer syndromes, Yale Cancer Center (YCC) scientists have found the cancers are driven by a breakdown in how cells repair their DNA.07/18/2018
Source: Kidney Cancer Association - Category: Urology & Nephrology Source Type: news
CONCLUSIONS: There was no evidence of increased risk of developing dMMR CRC after CCY although a borderline significantly increased 2-fold risk was observed 10-20 years after CCY. Larger studies are warranted to examine this further. PMID: 30010450 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
(University of Toronto) New fundamental complex in cells drives 'messy' form of DNA repair. In immune cells, this is crucial to make antibodies. In cancer, mutations in complex could lead to resistance to BRCA-targeting PARP inhibitor drugs or platinum chemotherapies.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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