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Profile Name ATM del
Gene Variant Detail

ATM del (loss of function)

Relevant Treatment Approaches Olaparib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
ATM S1455R neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm S1455R, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM R3008H esophagus small cell carcinoma predicted - sensitive Etoposide + Olaparib Case Reports/Case Series Actionable In a clinical case study, the combination of Lynparza (olaparib) and Vepesid (etoposide) resulted in a partial response and 5.9 months of progression-free survival in a patient with small cell esophageal carcinoma harboring ATM R3008H (PMID: 35480123). 35480123
ATM R1882* ATM R3008H pancreatic cancer predicted - sensitive Berzosertib + Irinotecan Case Reports/Case Series Actionable In a Phase I trial, the combination of Berzosertib (VX-970) and Camptosar (irinotecan) was tolerated in patients with advanced solid tumors, and resulted in a partial response that was ongoing at 11 months in a pancreatic cancer patient harboring ATM R3008H and germline ATM R1882* (J Clin Oncol 40, 2022 (suppl 16; abstr 3012); NCT02595931). detail...
ATM V410A lung small cell carcinoma predicted - sensitive Temozolomide + Veliparib Case Reports/Case Series Actionable In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted stable disease in a patient with small cell lung cancer harboring ATM V410A, with a progression-free survival of 6.3 months and an overall survival of 6.3 months (PMID: 29906251; NCT01638546). 29906251
ATM over exp stomach cancer decreased response Veliparib Preclinical - Cell culture Actionable In a preclinical study, high ATM expression was associated with decreased response to Veliparib (ABT-888) in gastric cancer cell lines in culture (PMID: 27638859). 27638859
ATM over exp stomach cancer decreased response Irinotecan Preclinical - Cell culture Actionable In a preclinical study, high ATM expression was associated with decreased response to Camptosaur (irinotecan) in gastric cancer cell lines in culture (PMID: 27638859). 27638859
ATM over exp stomach cancer sensitive Irinotecan + Veliparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Camptosar (irinotecan) and Veliparib (ABT-888) demonstrated synergy in gastric cancer cell lines with high ATM expression, resulting in increased apoptosis in culture, and enhanced tumor growth inhibition in cell line xenograft models (PMID: 27638859). 27638859
ATM P1069fs ATM LOH salivary gland adenoid cystic carcinoma predicted - sensitive Ceralasertib + Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing 22% reduction in target lesions in a patient with adenoid cystic carcinoma of minor salivary gland harboring germline ATM P1069fs with accompanying loss of heterozygosity (LOH), who remained on treatment for over 26 months (PMID: 34527850; NCT02576444). 34527850
ATM S333F lung small cell carcinoma predicted - sensitive Temozolomide + Veliparib Case Reports/Case Series Actionable In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted stable disease in a patient with small cell lung cancer harboring ATM S333F, with a progression-free survival of 4.2 months and an overall survival of 4.2 months (PMID: 29906251; NCT01638546). 29906251
ATM R2691C neuroblastoma no benefit Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of transformed neuroblastoma cells expressing ATM R2691C resulted in similar cell viability levels to wild-type Atm in culture (PMID: 29059438). 29059438
ATM S824F neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm S824F, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM I2629fs ATM neg endometrial clear cell adenocarcinoma predicted - sensitive BAY1895344 Case Reports/Case Series Actionable In a Phase I trial, BAY1895344 treatment resulted in a partial response with a 53% decrease in tumor size in a patient with clear cell endometrial cancer harboring ATM I2629fs with ATM protein loss, treatment was ongoing at 433 days (PMID: 32988960; NCT03188965). 32988960
ATM V1841I neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm V1841I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM D2725G lung small cell carcinoma predicted - sensitive Temozolomide + Veliparib Case Reports/Case Series Actionable In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted in partial response in a patient with small cell lung cancer harboring ATM D2725G, with a progression-free survival of 9 months and an overall survival of 16 months (PMID: 29906251; NCT01638546). 29906251
ATM loss chronic lymphocytic leukemia sensitive Ceralasertib + Ibrutinib Preclinical Actionable In a preclinical study, AZD6738 sensitized ATM-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). 26563132
ATM loss lung non-small cell carcinoma sensitive Ceralasertib + Cisplatin Preclinical Actionable In a preclinical study, AZD6738 and Platinol (cisplatin) synergistically induced cell death in ATM-deficient non-small cell lung carcinoma cell lines in culture, and caused rapid tumor regression in xenograft models (PMID: 26517239). 26517239
ATM loss Advanced Solid Tumor sensitive YU238259 Preclinical Actionable In a preclinical study, YU238259 demonstrated increased cytotoxicity in ATM-deficient transformed human cell lines in culture (PMID: 26116172). 26116172
ATM loss chronic lymphocytic leukemia sensitive AZD6482 Preclinical Actionable In a preclinical study, AZD6482 induced cell death in ATM-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). 26563132
ATM loss colorectal cancer sensitive Berzosertib Phase I Actionable In a Phase I trial, Berzosertib (VX-970) treatment resulted in complete response for more than 19 months in a colorectal cancer patient harboring ATM loss (J Clin Oncol 34, 2016 (suppl; abstr 2504)). detail...
ATM loss head and neck cancer predicted - sensitive Ceralasertib + Olaparib Preclinical - Cell culture Actionable In a preclinical study, the combination of AZD6738 and Lynparza (olaparib) resulted in a synergistic effect, demonstrating cell death in head and neck cancer cells harboring ATM loss in culture (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C60). detail...
ATM A59S neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm A59S, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM del prostate cancer no benefit Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, ATM-deficient prostate cancer cell lines did not respond to treatment with Lynparza (olaparib) in culture (PMID: 32127357). 32127357
ATM del lung non-small cell carcinoma sensitive AZD7648 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), inducing cell cycle arrest and inhibiting viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977). 31699977
ATM del head and neck cancer sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment induced genomic instability, cell cycle arrest, and inhibited viability of an ATM knockout head and neck cancer cell line in culture (PMID: 31699977). 31699977
ATM del head and neck cancer sensitive AZD7648 + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), resulting in inhibition of Dna-pk phosphorylation, reduced cell viability, genomic instability, cell cycle arrest, and apoptosis in a head and neck cancer cell line with ATM deletion in culture, and inhibition of tumor growth and complete tumor regression in a cell line xenograft model (PMID: 31699977). 31699977
ATM del prostate cancer sensitive Berzosertib Preclinical - Cell culture Actionable In a preclinical study, ATM-deficient prostate cancer cell lines were sensitive to treatment with Berzosertib (VX-970) in culture, demonstrating inhibition of cell growth (PMID: 32127357). 32127357
ATM del prostate cancer no benefit Rucaparib Preclinical - Cell culture Actionable In a preclinical study, ATM-deficient prostate cancer cell lines did not respond to treatment with Rubraca (rucaparib) in culture (PMID: 32127357). 32127357
ATM del lung non-small cell carcinoma sensitive AZD7648 Preclinical - Cell culture Actionable In a preclinical study, AZD7648 treatment inhibited viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977). 31699977
ATM del head and neck cancer sensitive AZD7648 Preclinical - Cell culture Actionable In a preclinical study, AZD7648 treatment induced genomic instability, cell cycle arrest, and inhibited viability of an ATM knockout head and neck cancer cell line in culture (PMID: 31699977). 31699977
ATM del lung non-small cell carcinoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment inhibited viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977). 31699977
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
ATM H2038Y neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm H2038Y, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM V519I neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm V519I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM K2749I neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm K2749I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM inact mut lymphoid leukemia sensitive Olaparib Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, lymphoblastoid cell lines with ATM inactivation derived from ataxia-telangiectasia patients demonstrated increased sensitivity to Lynparza (olaparib) in culture, compared to ATM wild-type cell lines (PMID: 20739657). 20739657
ATM inact mut Advanced Solid Tumor predicted - sensitive BAY1895344 Phase I Actionable In a Phase I trial, BAY1895344 treatment was tolerated and resulted in an objective response rate of 36.4% (4/11, all partial responses) and a disease control rate of 63.6% (7/11) in patients with advanced solid tumors harboring ATM inactivating mutations and/or ATM protein expression loss (PMID: 32988960; NCT03188965). 32988960
ATM inact mut chronic lymphocytic leukemia sensitive Olaparib Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived chronic lymphocytic leukemia cells with inactivating mutations in ATM, that had been induced to proliferate in culture, demonstrated increased sensitivity to growth inhibition by Lynparza (olaparib) compared to ATM wild-type cells (PMID: 20739657). 20739657
ATM inact mut mantle cell lymphoma sensitive Olaparib + Valproic acid Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and valproic acid worked synergistically to inhibit growth of a mantle cell lymphoma cell line harboring an ATM inactivating mutation in culture (PMID: 20739657). 20739657
ATM inact mut mantle cell lymphoma sensitive Olaparib Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, a mantle cell lymphoma cell line with ATM inactivation demonstrated sensitivity to Lynparza (olaparib) in culture and in xenograft models (PMID: 20739657). 20739657
ATM inact mut mantle cell lymphoma sensitive Bendamustine + Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Treanda (bendamustine) in cell culture, resulting in growth inhibition (PMID: 20739657). 20739657
ATM inact mut prostate cancer sensitive Olaparib Olaparib Phase II Actionable In a Phase II (TOPARP-B) trial, Lynparza (olaparib) treatment resulted in a composite overall response rate of 36.8% (7/19) and a RECIST objective response rate of 8.3% (1/12) in patients with castration-resistant prostate cancer harboring deleterious ATM mutations (PMID: 31806540; NCT01682772). 31806540
ATM inact mut prostate cancer sensitive Olaparib Olaparib Phase II Actionable In a Phase II clinical trial, 80% (4/5) of metastatic, castration-resistant prostate cancer patients harboring an ATM inactivating mutation responded to Lynparza (olaparib) (PMID: 26510020). 26510020
ATM inact mut prostate cancer sensitive Olaparib Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in ATM (NCCN.org). detail...
ATM inact mut prostate cancer sensitive Olaparib Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment improved progression-free survival (7.4 vs 3.6 mo, HR=0.34, p<0.001), objective response rate (33%, 28/84 vs 2%, 1/43, OR=20.86, p<0.001), and median time to pain progression (HR=0.44, p=0.02) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in BRCA1/2 or ATM who progressed on hormone therapy (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM inact mut Advanced Solid Tumor sensitive Veliparib Preclinical - Cell culture Actionable In a preclinical study, an ATM-deficient cell line demonstrated increased sensitivity to Veliparib (ABT-888) compared to an ATM-reconstituted cell line, in culture (PMID: 21300883). 21300883
ATM inact mut prostate cancer predicted - sensitive Abiraterone + Niraparib + Prednisone Phase III Actionable In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) significantly improved radiographic progression-free survival (16.5 vs 13.7 mo, HR 0.73, p=0.0217) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring alterations in homologous recombination repair genes including ATM, BRCA1/2, BRIP1, CHEK2, FANCA, HDAC2, and PALB2 (J Clin Oncol 40, 2022 (suppl 6; abstr 12); NCT03748641). detail...
ATM inact mut mantle cell lymphoma sensitive Fludarabine + Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Fludara (fludarabine) in cell culture, resulting in decreased cell survival (PMID: 20739657). 20739657
ATM inact mut prostate cancer no benefit Rucaparib Phase II Actionable In a Phase II trial (TRITON2), activity of Rubraca (rucaparib) was limited in the cohort of patients with metastatic castrate-resistant prostate cancer harboring an ATM mutation presumed to be inactivating, with a radiographic response rate of 10.5% (2/19, including 1 patient with co-occurring CHEK2 alteration) and PSA response rate of 4.1% (2/49), and no radiographic responses in 11 patients with biallelic alterations in ATM or 11 patients with germline ATM alterations (PMID: 32086346; NCT02952534). 32086346
ATM inact mut Advanced Solid Tumor predicted - sensitive Ceralasertib + Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an overall response rate of 20% (1/5) and a clinical benefit rate of 40% (2/5) in patients with advanced solid tumors harboring ATM inactivating mutations, including a durable complete response in a patient with breast cancer and a durable stable disease in a patient with adenoid cystic carcinoma of minor salivary gland (PMID: 34527850; NCT02576444). 34527850
ATM inact mut Advanced Solid Tumor sensitive E7449 Preclinical Actionable In a preclinical study, E7449 inhibited proliferation of a ATM-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair pathway mutations (PMID: 26513298). 26513298
ATM inact mut Advanced Solid Tumor predicted - sensitive Radiotherapy Clinical Study Actionable In a clinical study, treatment with radiotherapy resulted in greater therapeutic efficacy in advanced solid tumor patients harboring an ATM inactivating mutation (n=177) compared to those who harbored an ATM variant of unknown significance (n=180), demonstrating a significantly decreased 2-year cumulative incidence of irradiated progression, 13.2% versus 27.5% (p=0.001), respectively, and the greatest clinical benefit was observed in tumors with bi-allelic ATM inactivating mutations (PMID: 32726432). 32726432
ATM LOH ATM inact mut estrogen-receptor positive breast cancer predicted - sensitive Ceralasertib + Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing complete response for over 26 months in a patient with estrogen receptor–positive metastatic breast cancer harboring germline ATM mutation with accompanying loss of heterozygosity (LOH) (PMID: 34527850; NCT02576444). 34527850
ATM negative collecting duct carcinoma predicted - sensitive BAY1895344 Case Reports/Case Series Actionable In a Phase I trial, BAY1895344 treatment resulted in a partial response with a 69% decrease in tumor size in a patient with renal collecting duct carcinoma harboring ATM protein loss, treatment was ongoing at 385 days (PMID: 32988960; NCT03188965). 32988960
ATM negative stomach cancer no benefit Olaparib + Paclitaxel Phase III Actionable In a Phase III trial (GOLD), addition of Lynparza (olaparib) to Taxol (paclitaxel) did not significantly improve overall survival (12.0 vs 10.0 months, HR=0.73, p=0.25) compared to Taxol (paclitaxel) alone in Asian patients with ATM-negative gastric cancer (PMID: 29103871; NCT01924533). 29103871
ATM negative stomach cancer predicted - sensitive Ceralasertib + Durvalumab Phase II Actionable In a Phase II trial, Ceralasertib (AZD6738) and Imfinzi (durvalumab) combination therapy resulted in an overall response rate of 22.6% (7/31, all partial responses), disease control rate of 58.1%, and median progression-free survival (mPFS) of 3.0 mo in advanced gastric cancer patients, with improved mPFS (5.60 vs 1.65 mo; HR 0.13, p<0.001) in patients with ATM protein loss and/or homologous repair deficiency (HRD) compared to those with intact ATM expression or HR proficiency (PMID: 35790315; NCT03780608). 35790315
ATM negative Advanced Solid Tumor predicted - sensitive BAY1895344 Phase I Actionable In a Phase I trial, BAY1895344 treatment was tolerated and resulted in an objective response rate of 36.4% (4/11, all partial responses) and a disease control rate of 63.6% (7/11) in patients with advanced solid tumors harboring ATM inactivating mutations and/or ATM protein expression loss (PMID: 32988960; NCT03188965). 32988960
ATM T2333fs ATM neg Her2-receptor negative breast cancer predicted - sensitive BAY1895344 Case Reports/Case Series Actionable In a Phase I trial, BAY1895344 treatment resulted in a partial response with a 54% decrease in tumor size in a patient with heavily treated, hormone receptor-positive, ERBB2 (HER2)-negative breast cancer harboring ATM T2333fs and ATM protein loss, who remained on treatment for 349 days (PMID: 32988960; NCT03188965). 32988960
ATM I1294Nfs*8 ATM E2977Rfs*2 colorectal adenocarcinoma predicted - sensitive Irinotecan + Olaparib Case Reports/Case Series Actionable In a clinical case study, Lynparza (olaparib) and Camptosar (irinotecan) combination treatment resulted in decreased tumor markers and stable disease in the primary and metastatic tumors in a heavily pretreated patient with metastatic colorectal adenocarcinoma harboring ATM E2977Rfs*2, ATM I1294Nfs*8, and KRAS G13D, lasting at least 4 months (PMID: 35004311). 35004311
ATM L804fs ATM S978fs RET M918T thyroid gland medullary carcinoma predicted - sensitive Everolimus + Vandetanib Case Reports/Case Series Actionable In a clinical case study, addition of Afinitor (everolimus) to Caprelsa (vandetanib) treatment resulted in significant tumor reduction in a medullary thyroid carcinoma patient harboring ATM L804fs*4, ATM S978fs*12, and RET M918T, that achieved prolonged stable disease on Caprelsa (vandetanib) treatment alone (PMID: 27683183). 27683183
ATM dec exp stomach cancer predicted - sensitive Olaparib + Paclitaxel Phase II Actionable In a Phase II trial, addition of Lynparza (olaparib) to Taxol (paclitaxel) did not significantly improve progression free survival (5.29 vs 3.68 months) compared to Taxol alone, but did significantly prolong overall survival (HR = 0.35) in metastatic gastric cancer patients with decreased Atm expression (PMID: 26282658; NCT01063517). 26282658
ATM dec exp stomach cancer sensitive Veliparib Preclinical - Cell line xenograft Actionable In a preclinical study, knockdown of ATM in a gastric cancer cell line resulted in increased sensitivity to Veliparib (ABT-888) in culture and in xenograft models (PMID: 27638859). 27638859
ATM dec exp breast cancer sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, knockdown of ATM expression sensitized breast cancer cells to treatment with Talzenna (talazoparib) in culture (PMID: 23881923). 23881923
ATM T1200Lfs*7 NRAS Q61K TP53 R213* sarcoma predicted - resistant Olaparib Olaparib Case Reports/Case Series Actionable In a clinical case study, Lynparza (olaparib) treatment resulted in rapid disease progression in a patient with high-grade sarcoma harboring ATM T1200Lfs*7, NRAS Q61K, and TP53 R213* (PMID: 29304353). 29304353
ATM L1956H neuroblastoma no benefit Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm L1956H, resulted in similar cell viability levels as cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM P960H neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm P960H, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM P604S neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm P604S, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
ATM L1449* prostate adenocarcinoma predicted - sensitive Olaparib Olaparib Case Reports/Case Series Actionable In a clinical case study, Lynparza (olaparib) treatment resulted in stable disease for more than 6 months in a patient with prostate adenocarcinoma harboring ATM L1449*, amplification of AR, MYC, BCL9, MCL1, MDM4, RPS6KB1, APEX1, PNP, ATP11B, and DCUN1D1, and a TMPRSS2-ERG fusion (PMID: 29304353). 29304353
ATM S214fs colorectal cancer predicted - sensitive Berzosertib + Irinotecan Case Reports/Case Series Actionable In a Phase I trial, the combination of Berzosertib (VX-970) and Camptosar (irinotecan) was tolerated in patients with advanced solid tumors, and resulted in a 26% tumor decrease lasting 7.5 months in a colorectal cancer patient harboring ATM S214fs (J Clin Oncol 40, 2022 (suppl 16; abstr 3012); NCT02595931). detail...
ATM R3008C pancreatic ductal adenocarcinoma no benefit Fluorouracil + Oxaliplatin + Veliparib Case Reports/Case Series Actionable In a Phase I/II trial, Veliparib (ABT-888) in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) did not result in a clinical response in a patient with metastatic pancreatic ductal adenocarcinoma harboring ATM R3008C (PMID: 32669374; NCT01489865). 32669374
ATM T2333Nfs*40 pancreatic ductal adenocarcinoma no benefit Fluorouracil + Oxaliplatin + Veliparib Case Reports/Case Series Actionable In a Phase I/II trial, Veliparib (ABT-888) in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) did not result in a clinical response in a patient with metastatic pancreatic ductal adenocarcinoma harboring ATM T2333Nfs*40 (reported as c.6997dupA) (PMID: 32669374; NCT01489865). 32669374
ATM mutant prostate cancer sensitive Olaparib Olaparib Phase II Actionable In a Phase II clinical trial, 80% (4/5) of metastatic castration-resistant prostate cancer patients with ATM truncation mutations demonstrated response to Lynparza (olaparib) treatment (Cancer Res August 1, 2015 75:CT322). detail...
ATM mutant mantle cell lymphoma predicted - sensitive Ibrutinib + Venetoclax Phase II Actionable In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). 30455436
ATM mutant prostate cancer not applicable N/A Guideline Risk Factor Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org). detail...
ATM mutant breast cancer no benefit Olaparib Olaparib Case Reports/Case Series Actionable In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 4 patients with metastatic breast cancer harboring only germline mutations in ATM (PMID: 33119476; NCT03344965). 33119476
ATM mut NRAS Q61R melanoma predicted - sensitive Binimetinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312). 28514312
ATM S1905Ifs*25 gallbladder carcinoma predicted - sensitive Olaparib Olaparib Case Reports/Case Series Actionable In a clinical case study, treatment with Lynparza (olaparib) resulted in improved clinical symptoms and progression-free survival of 13 months in a patient with gallbladder carcinoma harboring ATM S1905Ifs*25 (PMID: 32045060). 32045060
ATM positive lung cancer sensitive AZD1390 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD1390 inhibited Atm activity, sensitized lung cancer cells to radiotherapy in culture, and demonstrated efficacy in cell line xenograft models (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). detail...
ATM positive glioblastoma sensitive AZD1390 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD1390 inhibited Atm activity, sensitized glioblastoma cell lines to radiotherapy in culture, and demonstrated efficacy in mouse models of glioblastoma (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). detail...
ATM V1268fs appendix cancer predicted - sensitive BAY1895344 Case Reports/Case Series Actionable In a Phase I trial, BAY1895344 treatment resulted in a partial response with a 35% decrease in tumor size in a patient with appendix cancer harboring ATM T2333fs, treatment was ongoing at 472 days (PMID: 32988960; NCT03188965). 32988960
ATM L1874F neuroblastoma sensitive Olaparib Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm L1874F, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438). 29059438
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02264678 Phase Ib/II Ceralasertib Carboplatin + Ceralasertib Ceralasertib + Durvalumab Ceralasertib + Olaparib Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents Recruiting USA | FRA 2
NCT03810105 Phase II Durvalumab + Olaparib A Study of Olaparib and Durvalumab in Prostate Cancer Active, not recruiting USA 0
NCT03840967 Phase II Niraparib A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma Recruiting USA 0
NCT02518555 Phase II Ibrutinib Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Active, not recruiting USA 0
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