The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system is a powerful tool that enables precise and efficient gene manipulation. In a relatively short time, CRISPR has risen to become the preferred gene-editing system due to its high efficiency, simplicity, and programmability at low costs. Furthermore, in the recent years, the CRISPR toolkit has been rapidly expanding, and the emerging advancements have shown tremendous potential in uncovering molecular mechanisms and new therapeutic strategies for human diseases. In this review, we provide our perspectives on the recent advancements in CRISPR technology and its impact on precision medicine, ranging from target identification, disease modeling, and diagnostics. We also discuss the impact of novel approaches such as epigenome, base, and prime editing on preclinical cancer drug discovery.
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http://dx.doi.org/10.3389/fgene.2023.1273994 | DOI Listing |
J Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Massachusetts General Hospital Cancer Center, Boston, MA, United States.
Background: Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC.
Methods: A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted.
Endocrine
January 2025
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
The word "cancer" evokes myriad emotions, ranging from fear and despair to hope and determination. Cancer is aptly defined as a complex and multifaceted group of diseases that has unapologetically led to the loss of countless lives and affected innumerable families across the globe. The battle with cancer is not only a physical battle, but also an emotional, as well as a psychological skirmish for patients and for their loved ones.
View Article and Find Full Text PDFEur J Trauma Emerg Surg
January 2025
Emergency Department, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel.
Objective: To evaluate the NEXUS Chest CT ALL decision instrument (DI) in reducing unnecessary chest CT imaging in minor blunt trauma patients while preserving high sensitivity for detecting clinically meaningful injuries. Additionally, we examined the impact of delayed presentation, chronic disease, and anticoagulation/anti-aggregation medications on trauma outcomes.
Methods: This retrospective study included 853 adult minor blunt trauma patients who underwent chest CT in the emergency department (ED) of Tel-Aviv Sourasky Medical Center between 2018 and 2022.
Neurosci Bull
January 2025
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, College of Pharmaceutical Sciences, The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital), Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis.
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