Publications by authors named "D J McGrail"
Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells.
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- Researchers suggest a new network-based method to identify immunomodulatory genetic variants linked to COVID-19 by analyzing protein interaction networks.
- They discovered that variants affecting specific protein interactions can significantly impact immune response, even if they don't reach usual statistical significance in genome-wide studies.
- Their findings highlight the importance of myeloid and T cell subsets in the immune response and point out a specific variant that disrupts a key protein interaction related to interferon signaling.
Transcutaneous aortic valve replacement (TAVR) has evolved from a complex procedure meant only for patients at prohibitive risk for surgery to a commonly performed procedure across a wide variety of clinical scenarios including the treatment of failed aortic valve bioprosthesis. Annuloplasty rings in the aortic position such as HAART 300 (Biostable Science and Engineering) have been introduced in the management of native aortic regurgitation. Percutaneous management of failed bioprosthesis rings in the aortic position has not been widely described.
View Article and Find Full Text PDFPurpose: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.
Experimental Design: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models.
Article Synopsis
- Pharmacological inhibition of ATR (Ataxia Telangiectasia and Rad3-related protein) is showing promise for cancer treatment by targeting DNA damage repair pathways, helping to overcome resistance to therapies, and boosting anti-tumor immunity.
- Multiple novel ATR inhibitors are currently being tested in clinical trials across various solid tumors, with some reaching phase III trials, but more research is needed to understand their interactions with DNA repair and the immune system.
- Key challenges in developing ATR inhibitors include improving their effectiveness, identifying the right patient populations through predictive biomarkers, and creating effective drug combinations to maximize therapeutic benefits.