Identification of Cell Nonautonomous DNA Damage Responses in the Tumor Microenvironment that Contribute to Cancer Therapy Resistance

2014 ◽  
Author(s):  
Ryan R. Gordon
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapy Resistance ◽  
Dna Damage Responses

scholarly journals Role of hypoxia in cancer therapy by regulating the tumor microenvironment

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinming Jing ◽  
Fengming Yang ◽  
Chuchu Shao ◽  
Ke Wei ◽  
Mengyan Xie ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Web Of Science ◽  
Therapy Resistance ◽  
Mitochondrial Activity ◽  
Cellular Expression ◽  
Clinical Resistance ◽  
Expression Program

Abstract Aim Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. Methods Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms. Results Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux. Conclusion Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.

scholarly journals Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kenta Yamamoto ◽  
Jiguang Wang ◽  
Lisa Sprinzen ◽  
Jun Xu ◽  
Christopher J Haddock ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Therapy ◽  
Animal Models ◽  
Dna Adducts ◽  
Kinase Domain ◽  
Missense Mutations ◽  
Atm Kinase ◽  
Dna Damage Responses ◽  
Atm Protein ◽  
Kinase A

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

Abstract A04: Targeting immunosuppressive alterations in the tumor microenvironment resulting from therapy-induced DNA damage responses

2016 ◽  
Author(s):  
Wei Jin ◽  
Aric Zhao ◽  
Christine Levesque ◽  
Ilsa Colman ◽  
Peter S. Nelson
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Dna Damage Responses

scholarly journals Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B

2012 ◽  
Vol 18 (9) ◽  
pp. 1359-1368 ◽  
Author(s):  
Yu Sun ◽  
Judith Campisi ◽  
Celestia Higano ◽  
Tomasz M Beer ◽  
Peggy Porter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapy Resistance ◽  
Prostate Cancer Therapy
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