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Ceralasertib (AZD6738) is an oral, potent, and selective small molecule inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein. ATR is a key regulator of the DNA damage response, particularly in sensing replication stress and single-strand DNA breaks. By inhibiting ATR, ceralasertib prevents tumor cells from repairing DNA damage, leading to genomic instability and apoptosis. In clinical studies conducted by the Samsung Medical Center, ceralasertib is evaluated in combination with paclitaxel, a microtubule-stabilizing agent that interferes with mitosis. This combination therapy is designed to exploit synthetic lethality and potentiate the cytotoxic effects of chemotherapy in patients with refractory advanced solid malignancies, including those who have failed prior anti-PD-1/PD-L1 immunotherapy.
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