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Gene Symbol | ATR | ||||||||||
Synonyms | FCTCS | FRP1 | MEC1 | SCKL | SCKL1 | ||||||||||
Gene Description | ATR, ATR serine/threonine kinase, is involved in regulation of the DNA damage response and mediation of cell-cycle checkpoints (PMID: 25512053). Loss of function ATR mutations have been identified in melanoma (PMID: 28273450), and inhibition of Atr selectively sensitizes cancerous cells to radiation and chemotherapy (PMID: 23583268, PMID: 31836456, PMID: 29054375). | ||||||||||
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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ATR over exp | chronic lymphocytic leukemia | predicted - sensitive | Ceralasertib | Preclinical | Actionable | In a preclinical study, chronic lymphocytic leukemia cells expressing ATR were sensitive to AZD6738 (Cancer Res October 1, 2014 74; 5485). | detail... |
ATR inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved | Actionable | In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including ATR, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). | detail... 37285865 |
ATR inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | Guideline | Actionable | Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATR mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). | detail... |
ATR positive | breast cancer | predicted - sensitive | VE-821 | Preclinical - Cell culture | Actionable | In a preclinical study, human breast cancer cell lines demonstrated sensitivity to VE-821 in culture, resulting in decreased cell survival (PMID: 25468710). | 25468710 |
ATR positive | lung cancer | sensitive | Berzosertib + Cisplatin | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Berzosertib (VX-970) sensitized patient-derived lung cancer cells to Platinol (cisplatin) in culture and in patient-derived xenograft (PDX) models (PMID: 25010037). | 25010037 |
ATM del ATR dec exp | Advanced Solid Tumor | decreased response | PJ34 | Preclinical - Cell culture | Actionable | In a preclinical study, ATM-null transformed cells with decreased Atr expression demonstrated decreased sensitivity to PJ34 in culture (PMID: 21840268). | 21840268 |
ATR del | colorectal cancer | sensitive | E7820 | Preclinical - Cell culture | Actionable | In a preclinical study, E7820 inhibited viability of a colorectal cancer cell line with knockout of ATR in culture (PMID: 38789724). | 38789724 |
ATR del | colorectal cancer | sensitive | Indisulam | Preclinical - Cell culture | Actionable | In a preclinical study, Indisulam (E7070) inhibited viability of a colorectal cancer cell line with knockout of ATR in culture (PMID: 38789724). | 38789724 |