Ceralasertib + AZD5305

Ceralasertib + AZD5305 is an investigational oral combination therapy being studied primarily for advanced solid tumors, including ovarian, breast, and pancreatic cancers. Ceralasertib (also known as AZD6738) is a selective inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), a key regulator of the DNA damage response pathway. By inhibiting ATR, ceralasertib impairs cancer cells' ability to repair DNA damage, leading to cell death. AZD5305 is a next-generation small molecule that selectively inhibits poly(ADP-ribose) polymerase 1 (PARP1), with over 500-fold selectivity for PARP1 over PARP2. Inhibition of PARP1 further disrupts DNA repair in tumor cells with homologous recombination deficiencies such as BRCA mutations. The combination aims to enhance antitumor activity by simultaneously targeting two critical components of the DNA damage response pathway, potentially overcoming resistance mechanisms seen with single-agent therapies[2][3][5][6]. Both agents are developed by AstraZeneca.