Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.7314/apjcp.2014.15.16.6485 | DOI Listing |
Sci Rep
December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads to mechanical vulnerability of cancer cells, causing nuclear envelope softness and collapse and activation of the cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with the non-canonical role of ATR in controlling nuclear mechanics presents an intriguing therapeutic opportunity.
View Article and Find Full Text PDFExpert Opin Ther Pat
December 2024
P. Hertsen Moscow Oncology Research Institute, Moscow, Russian Federation.
Introduction: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials.
Areas Covered: This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors.
J Adv Res
December 2024
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address:
Introduction: The efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
October 2024
School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 211198, China.
In order to study the effect of the simplified formula of Jinfukang Oral Liquid(ALG-12) on renal tubular injury induced by cisplatin(DDP), 48 C57 mice were divided into control group, model group, DDP group, and DDP combined with low, medium, and high dose groups of ALG-12. The mice were administered for 16 days after the establishment of the subcutaneous Lewis lung cancer heterotopic transplant tumor model of mice. The pathological changes, serum creatinine(Scr), blood urea nitrogen(BUN), kidney injury molecule 1(Kim-1), neutrophil gelatinase-associated lipocalin(NGAL), malondialdehyde(MDA), and total superoxide dismutase(T-SOD) in renal tissue and the degree of renal tubular cell apoptosis were analyzed to investigate the effect of ALG-12 on renal injury induced by DDP treatment on non-small cell lung cancer(NSCLC).
View Article and Find Full Text PDFBrain
December 2024
Department of Neuromuscular diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!