ATR and CHK1 inhibitors
Drugs that disable the checkpoint cancer cells use to pause and repair DNA under replication stress, pushing tumours with faulty DNA repair into collapse.
Overview
ATR and its downstream kinase CHK1 halt the cell cycle when DNA replication stalls. Tumours with ATM loss, high replication stress from oncogenes or defective homologous recombination depend on this checkpoint, and inhibitors such as ceralasertib, camonsertib and berzosertib have shown activity in these settings and in combination with PARP inhibitors, chemotherapy and immunotherapy. Anaemia and neutropenia limit continuous dosing, so intermittent schedules are used; no agent is approved yet.
How it works
ATP-competitive kinase inhibitors block ATR or CHK1 signalling so that cells with damaged or under-replicated DNA enter mitosis and die.
- Exploits synthetic lethality with ATM loss and replication stress
- Combines with PARP inhibitors and radiotherapy
- Haematological toxicity
- Biomarkers still being defined
- No approval
Latest papers
topQuery for this technology: (TITLE:"ATR and CHK1 inhibitors" OR ABSTRACT:"ATR and CHK1 inhibitors") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ATR and CHK1 inhibitors, not a curated reading list.
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