ART0380 + gemcitabine

ART0380 + gemcitabine is a combination of two anticancer agents being clinically investigated for the treatment of advanced or metastatic solid tumors, particularly ovarian cancer. ART0380 is an orally administered, selective small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), a kinase involved in DNA damage response and replication stress signaling. By inhibiting ATR, ART0380 impairs DNA repair in cancer cells experiencing high replication stress, increasing the cytotoxicity of DNA-damaging chemotherapy. Gemcitabine is a widely used nucleoside analog and DNA synthesis inhibitor that induces DNA damage by incorporation into DNA and inhibition of DNA polymerase. The combination exploits synergistic effects: gemcitabine induces DNA damage, while ART0380 inhibits the repair mechanism, resulting in enhanced cancer cell death. This regimen is being evaluated in a phase 1/2 clinical trial for patients with ovarian cancers, and is also studied for activity in multiple other solid tumors, particularly those with ATM gene alterations[5][2][3].