AI Article Synopsis
- The initial discovery of DNA damaging agents like mustard gas led to the development of chemotherapy drugs that have antitumor properties, although they often harm healthy cells.
- Recent advancements focus on targeting cancer cells by exploiting their DNA damage through compounds that affect the replication stress-response, specifically using inhibitors of the ATR protein.
- As ATR inhibitors enter clinical trials, there is an emphasis on understanding patient selection and identifying biomarkers that could predict better responses to this targeted therapy.
Article Abstract
The chemical treatment of cancer started with the realization that DNA damaging agents such as mustard gas present notable antitumoural properties. Consequently, early drug development focused on genotoxic chemicals, some of which are still widely used in the clinic. However, the efficacy of such therapies is often limited by the side effects of these drugs on healthy cells. A refinement to this approach is to use compounds that can exploit the presence of DNA damage in cancer cells. Given that replication stress (RS) is a major source of genomic instability in cancer, targeting the RS-response kinase ataxia telangiectasia and Rad3-related protein (ATR) has emerged as a promising alternative. With ATR inhibitors now entering clinical trials, we here revisit the biology behind this strategy and discuss potential biomarkers that could be used for a better selection of patients who respond to therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41568-018-0034-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
How human papillomavirus (HPV) targets DNA repair pathways for viral replication: from guardian to accomplice.
Microbiol Mol Biol Rev
January 2025
Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA.
SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithelia at a variety of body locations and link their productive life cycles to the differentiation of the host cell. These viruses have evolved sophisticated mechanisms to exploit cellular pathways, such as DNA damage repair (DDR), to regulate their life cycles.
View Article and Find Full Text PDFIntegration of DNA replication with DNA repair, cell cycle progression, and other biological processes is crucial for preserving genome stability and fundamentally important for all life. Ataxia-telangiectasia mutated and RAD3-related (ATR) and its partner ATR-interacting protein (ATRIP) function as a critical proximal sensor and transducer of the DNA Damage Response (DDR). Several ATR substrates, including p53 and CHK1, are crucial for coordination of cell cycle phase transitions, transcription, and DNA repair when cells sustain DNA damage.
View Article and Find Full Text PDFSimultaneous Classification of Objects with Unknown Rejection (SCOUR) Using Infra-Red Sensor Imagery.
Sensors (Basel)
January 2025
Department of Electrical and Computer Engineering, University of Central Florida, Orlando, FL 32816-8005, USA.
Recognizing targets in infra-red images is an important problem for defense and security applications. A deployed network must not only recognize the known classes, but it must also reject any new or objects without confusing them to be one of the known classes. Our goal is to enhance the ability of existing (or pretrained) classifiers to detect and reject unknown classes.
View Article and Find Full Text PDFOlaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in -Mutated Epithelial Ovarian Cancer Cell Lines.
Int J Mol Sci
January 2025
Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland.
Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial-mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance.
View Article and Find Full Text PDFIdentification of Immune Infiltration-Associated CC Motif Chemokine Ligands as Biomarkers and Targets for Colorectal Cancer Prevention and Immunotherapy.
Int J Mol Sci
January 2025
Centre of Biomedical Systems and Informatics, ZJU-UoE Institute, School of Medicine, International Campus, Zhejiang University, Haining 314400, China.
Colorectal cancer (CRC) is the third most common cancer globally, with limited effective biomarkers and sensitive therapeutic targets. An increasing number of studies have highlighted the critical role of tumor microenvironment (TME) imbalances, particularly immune escape due to impaired chemokine-mediated trafficking, in tumorigenesis and progression. Notably, CC chemokines (CCLs) have been shown to either promote or inhibit angiogenesis, metastasis, and immune responses in tumors, thereby influencing cancer development and patient outcomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!