Abstract
Radiation therapy (RT) is widely used in cancer care strategies. Its effectiveness relies mainly on its ability to cause lethal damage to the DNA of cancer cells. However, some cancers have shown to be particularly radioresistant partly because of efficient and redundant DNA repair capacities. Therefore, RT efficacy might be enhanced by using drugs that can disrupt cancer cells' DNA repair machinery. Here we review the recent advances in the development of novel inhibitors of DNA repair pathways in combination with RT. A large number of these compounds are the subject of preclinical/clinical studies and target key enzymes involved in one or more DNA repair pathways. A totally different strategy consists of mimicking DNA double-strand breaks via small interfering DNA (siDNA) to bait the whole DNA repair machinery, leading to its global inhibition.
Highlights
Radiation therapy (RT), in conjunction with surgery and systemic therapies, is a cornerstone of cancer care
RT-induced cell death is mostly due to DNA damage, especially to double-strand breaks (DSBs) [6, 7]
One of the early steps is the phosphorylation of histone H2AX (γ-H2AX), which signals the presence of DSB to repair proteins where they aggregate in ionizing radiation-induced foci (IRIF) [42]
Summary
Radiation therapy (RT) is widely used in cancer care strategies. Its effectiveness relies mainly on its ability to cause lethal damage to the DNA of cancer cells. Some cancers have shown to be radioresistant partly because of efficient and redundant DNA repair capacities. RT efficacy might be enhanced by using drugs that can disrupt cancer cells’ DNA repair machinery. We review the recent advances in the development of novel inhibitors of DNA repair pathways in combination with RT. A large number of these compounds are the subject of preclinical/clinical studies and target key enzymes involved in one or more DNA repair pathways. A totally different strategy consists of mimicking DNA double-strand breaks via small interfering DNA (siDNA) to bait the whole DNA repair machinery, leading to its global inhibition
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