Ataxia-Telangiectasia Mutated (ATM) gene signaling pathways in human cancers and their therapeutic implications.

Cancer is a multifaceted disease driven by abnormal cell growth and poses a significant global health threat. The multifactorial causes, differences in individual susceptibility to therapeutic drugs, and induced drug resistance pose major challenges in addressing cancers effectively. One of the most important aspects in making cancers highly heterogeneous in their physiology lies in the genes involved and the changes occurring to some of these genes in malignant conditions. The Genetic factors have been implicated in the oncogenesis, progression, responses to treatment, and metastasis. One such gene that plays a key role in human cancers is the mutated form of the Ataxia-telangiectasia gene (ATM). ATM gene located on chromosome 11q23, plays a vital role in maintaining genomic stability. Understanding the genetic basis of A-T is crucial for diagnosis, management, and treatment. Breast cancer, lung cancer, prostate cancer, and gastric cancer exhibit varying relationships with the ATM gene and influence their pathways. Targeting the ATM pathway proves promising for enhancing treatment effectiveness, especially in conjunction with DNA damage response pathways. Analyzing the therapeutic consequences of ATM mutations, especially in these cancer types facilitates the approaches for early detection, intervention, development of personalized treatment approaches, and improved patient outcomes. This review emphasizes the role of the ATM gene in various cancers, highlighting its impact on DNA repair pathways and therapeutic responses.

Morin Protects Human Respiratory Cells from PM2.5 Induced Genotoxicity by Mitigating ROS and Reverting Altered miRNA Expression.

Chronic fine particulate matter (PM2.5) exposure causes oxidative stress and leads to many diseases in human like respiratory and cardiovascular disorders, and lung cancer. It is known that toxic responses elicited by PM2.5 particles depend on its physical and chemical characteristics that are greatly influenced by the source. Dietary polyphenolic compounds that possess antioxidant and free radical scavenging properties could be used for therapeutic or preventive approaches against air pollution related health hazards. This study evaluates characteristics and toxicity of PM2.5 collected from rural, urban, industrial, and traffic regions in and around Coimbatore City, Tamilnadu, India. Traffic PM2.5 particles contained higher amounts of metals and polycyclic aromatic hydrocarbons (PAHs). It also possessed higher levels of oxidative potential, induced more intracellular reactive oxygen species (ROS), and caused more levels of cell death and DNA damage in human respiratory cells. Its exposure up regulated DNA damage response related miR222, miR210, miR101, miR34a, and miR93 and MycN and suppressed Rad52. Pre-treatment with morin significantly decreased the PM2.5 induced toxicity and conferred protection against PM2.5 induced altered miRNA expression. Results of this study showed that cytoprotective effect of morin is due to its antioxidative and free radical scavenging activity.