Ataxia telangiectasia mutated (ATM) kinase controls key cell cycle checkpoints and the repair of DNA double strand breaks and has been considered an attractive intervention point in DNA damage response for cancer therapy. Here, Zimmermann et al. introduce two novel ATM inhibitors. These highly potent and selective small molecules effectively suppress the ATM pathway, enhance antitumor effect of radiation and topoisomerase I inhibitors and synergize with PARP inhibitors in cancer cells and animal models of human cancer. They represent new molecular tools with potential for combination with key cancer therapies.
ERα antagonists and degraders are highly effective in the treatment of the majority of ERα+ breast cancers but resistance mechanisms, including ERα mutations that facilitate ligand-independent activation, blunt the effectiveness of these therapies. Here, Furman et al. report on the development H3B-6545, a novel covalent inhibitor of ERa which demonstrates superiority over standard-of-care fulvestrant in both ERWT and ERα...
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