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

Related Links:

Discussion of the Evolutionary Genetics of Aging Thymic Involution Contributes to Immunosenescence and Inflammaging The Potential for Exosome Therapies to Treat Sarcopenia Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice The Aging Retina, a Mirror of the Aging Brain Evidence for Loss of Capillary Density to be Important in Heart Disease Aspects of Immune System Aging Proceed More Rapidly in Men Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation Transplantation of Senescent Cells is an ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions: Our findings demonstrate that Regorafenib enhanced radiosensitivity of breast cancer cells by inhibiting the expression of multiple receptor tyrosine kinases, VEGF-mediated angiogenesis and DNA damage response in TNBC. Therefore, combining Regorafenib with radiation and antiangiogenic agents will be beneficial and effective in controlling TNBC. PMID: 32052681 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein e...
Source: The Chinese Journal of Physiology - Category: Physiology Tags: Chin J Physiol Source Type: research
Authors: Garufi G, Palazzo A, Paris I, Orlandi A, Cassano A, Tortora G, Scambia G, Bria E, Carbognin L Abstract Introduction: Despite recent advances in the molecular characterization of triple-negative breast cancer (TNBC), the standard treatment for early-stage TNBC is represented by the historically used anthracycline and taxane-based chemotherapy. In this modern era of precision medicine, several new therapeutic strategies and novel agents have been investigated in the neoadjuvant setting of TNBC, in order to individualize treatment.Areas covered: This review provides a comprehensive overview of the currently a...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are th...
Source: eLife - Category: Biomedical Science Tags: Genetics and Genomics Source Type: research
AbstractThe advent of gene panel testing is challenging the previous practice of using clinically defined cancer family  syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have a pplied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 andPMS2) to an Australian population-based case –control-family study of breast cancer. Altogether, eig...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSION: Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. IMPLICATIONS FOR PRACTICE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Cancers, Vol. 12, Pages 453: A ”Clickable” Probe for Active MGMT in Glioblastoma Demonstrates Two Discrete Populations of MGMT Cancers doi: 10.3390/cancers12020453 Authors: Raghavan Baskin Sharpe Various pathways can repair DNA alkylation by chemotherapeutic agents such as temozolomide (TMZ). The enzyme O6-methylguanine methyltransferase (MGMT) removes O6-methylated DNA adducts, leading to the failure of chemotherapy in resistant glioblastomas. Because of the anti-chemotherapeutic activities of MGMT previously described, estimating the levels of active MGMT in cancer cells can be a significant pr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
The objective of this study was to evaluate B vitamins and methionine in relation to colorectal cancer risk in a Chinese population. A case-control study was conducted from July 2010 to April 2019. A total of 2502 patients with colorectal cancer were recruited along with 2538 age (5-year interval) and sex matched controls. Dietary data was collected by using a validated food frequency questionnaire. Multivariable logistic regression was used to assess odds ratios (ORs) and 95% confidence interval (CI). The intake of folate, vitamin B2, vitamin B6 and vitamin B12 was inversely associated with colorectal cancer risk. The mul...
Source: The British Journal of Nutrition - Category: Nutrition Authors: Tags: Br J Nutr Source Type: research
The ability of cancer cells to invade and disseminate can be affected by components of the surrounding microenvironment. To identify dermal components regulating the growth of epidermal carcinomas, we studied the xeroderma pigmentosum genetic disease that bears mutations in genes involved in nucleotide excision DNA repair. Xeroderma pigmentosum patients are more prone to develop cutaneous tumors compared to the general population and their dermal fibroblasts display features of dermal cancer-associated fibroblasts, promoting keratinocyte invasion.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
More News: Biology | Cancer | Cancer & Oncology | Cytology | Gastroschisis Repair