Daniela A. Dungl, Elaina N. Maginn, Euan A. Stronach
Abstract
Platinum-based chemotherapy is the cornerstone of ovarian cancer treatment, and its efficacy is dependent on the generation of DNA damage, with subsequent induction of apoptosis. Inappropriate or aberrant activation of the DNA damage response network is associated with resistance to platinum, and defects in DNA repair pathways play critical roles in determining patient response to chemotherapy. In ovarian cancer, tumor cell defects in homologous recombination - a repair pathway activated in response to double-strand DNA breaks (DSB) - are most commonly associated with platinum-sensitive disease. However, despite initial sensitivity, the emergence of resistance is frequent. Here, we review strategies for directly interfering with DNA repair pathways, with particular focus on direct inhibition of non-homologous end joining (NHEJ), another DSB repair pathway. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a core component of NHEJ and it has shown considerable promise as a chemosensitization target in numerous cancer types, including ovarian cancer where it functions to promote platinum-induced survival signaling, via AKT activation. The development of pharmacological inhibitors of DNA-PKcs is on-going, and clinic-ready agents offer real hope to patients with chemoresistant disease.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Other
5
10%
Unknown
6
12%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 November 2015.
All research outputs
#17,302,400
of 25,394,764 outputs
Outputs from Frontiers in oncology
#8,041
of 22,440 outputs
Outputs of similar age
#176,984
of 295,260 outputs
Outputs of similar age from Frontiers in oncology
#36
of 77 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 22,440 research outputs from this source. They receive a mean Attention Score of 3.0. This one has gotten more attention than average, scoring higher than 58% of its peers.
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We're also able to compare this research output to 77 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
