ceralasertib

Overview

Ceralasertib (AZD6738) is a selective ATP-competitive inhibitor of ATR (ataxia telangiectasia and RAD3-related) kinase, a key regulator of the DNA damage response (DDR) replication-stress checkpoint. It is under clinical development as monotherapy and in combinations with PARP inhibitors and chemotherapy across multiple tumor types. In the UCLA sarcoma PDTO screen, it showed the most significant differential sensitivity in osteosarcoma of any single agent.

Evidence in the corpus

• In the UCLA sarcoma PDTO biobank (sarcoma_ucla_2024, n=194 specimens from 126 patients across 24 subtypes), osteosarcoma PDTOs were significantly more sensitive than the pan-sarcoma average to ceralasertib (ATR inhibitor, p=0.00026) — the strongest statistical signal for any drug–subtype pair in the osteosarcoma sensitivity analysis, ahead of topotecan (p=0.028), cabozantinib (p=0.024), and everolimus (p=0.012). PMID:39305899

Resistance mechanisms

• Not characterized in the sarcoma corpus.

Cancer types (linked)

• OS — osteosarcoma; strongest differential sensitivity signal in pan-sarcoma PDTO screen (p=0.00026).

Sources

• PMID:39305899 — Al Shihabi et al. (Cell Stem Cell 2024). UCLA sarcoma PDTO biobank; ceralasertib identified as the top osteosarcoma-selective drug by p-value in the subtype sensitivity analysis.

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