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| Profile Name | ATM I2701Nfs*17 |
| Gene Variant Detail | |
| Relevant Treatment Approaches | PARP Inhibitor (Pan) |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| ATM H2038Y | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 P604S | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 P960H | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 over exp | stomach cancer | decreased response | PARP Inhibitor (Pan) | 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 | sensitive | PARP Inhibitor (Pan) | 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 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 negative | stomach cancer | no benefit | PARP Inhibitor (Pan) | 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 | 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 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 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 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 A59S | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 R3008C | pancreatic ductal adenocarcinoma | no benefit | PARP Inhibitor (Pan) | 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 T1200Lfs*7 NRAS Q61K TP53 R213* | sarcoma | predicted - resistant | PARP Inhibitor (Pan) | 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 R2691C | neuroblastoma | no benefit | PARP Inhibitor (Pan) | 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 L1449* | prostate adenocarcinoma | predicted - sensitive | PARP Inhibitor (Pan) | 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 L1874F | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 |
| 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 inact mut | lymphoid leukemia | sensitive | PARP Inhibitor (Pan) | 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 | prostate cancer | no benefit | PARP Inhibitor (Pan) | 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 | 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 inact mut | Advanced Solid Tumor | sensitive | PARP Inhibitor (Pan) | 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 | prostate cancer | sensitive | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | prostate cancer | sensitive | PARP Inhibitor (Pan) | 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 | mantle cell lymphoma | sensitive | PARP Inhibitor (Pan) | 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 | 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 | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | mantle cell lymphoma | sensitive | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | Advanced Solid Tumor | sensitive | PARP Inhibitor (Pan) | 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 K2749I | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 T2333Nfs*40 | pancreatic ductal adenocarcinoma | no benefit | PARP Inhibitor (Pan) | 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 V1841I | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 S333F | lung small cell carcinoma | predicted - sensitive | PARP Inhibitor (Pan) | 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 dec exp | stomach cancer | predicted - sensitive | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 L1956H | neuroblastoma | no benefit | PARP Inhibitor (Pan) | 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 S1455R | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 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 | sensitive | PARP Inhibitor (Pan) | 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 | 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 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 D2725G | lung small cell carcinoma | predicted - sensitive | PARP Inhibitor (Pan) | Temozolomide + Veliparib | Case Reports/Case Series | Actionable | In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted 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 V410A | lung small cell carcinoma | predicted - sensitive | PARP Inhibitor (Pan) | 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 S824F | neuroblastoma | sensitive | PARP Inhibitor (Pan) | 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 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 del | head and neck cancer | sensitive | PARP Inhibitor (Pan) | 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 | prostate cancer | no benefit | PARP Inhibitor (Pan) | 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 | 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 | head and neck cancer | sensitive | PARP Inhibitor (Pan) | 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 | no benefit | PARP Inhibitor (Pan) | 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 | PARP Inhibitor (Pan) | 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 | 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 | lung non-small cell carcinoma | sensitive | PARP Inhibitor (Pan) | 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 | 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 ATR dec exp | Advanced Solid Tumor | decreased response | PARP Inhibitor (Pan) | 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 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 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 loss | chronic lymphocytic leukemia | sensitive | AZD6738 + 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | AZD6738 + 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 | head and neck cancer | predicted - sensitive | PARP Inhibitor (Pan) | AZD6738 + 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... |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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