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CI-CAN-00000004Explore in graph →
Variants & evidence
7,750 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| ALK G1269A + ALK Fusion5 | ||||||||
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1342The NSCLC cell line MGH021-4, harboring SQSTM1-ALK G1269A, was 6 times more sensitive to ceritinib (80nM GI50) than crizotinib (500 nM) in proliferation assays and caused notable reductions in phospho… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1355EML4-ALK with G1269A mutation was tested for sensitivity to ceritinib via transduction into Ba/F3 cells and generation of survival curves varying ceritinib concentration. IC50 of 33 nM was seen, which… (full text at CIViC) PMID 25727400 · Fontana et al., 2015 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | submitted | EID4617In a non-small cell lung cancer patient with acquired crizotinib resistance, the tumor had an ALK gene rearrangement and an ALK G1269A co-mutation. The ALK G1269A tumor was reported to be refractory t… (full text at CIViC) PMID 23729361 · Gainor et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | submitted | EID4618In a non-small cell lung cancer patient with a bone metastatic tumor harboring an ALK gene rearrangement and an ALK G1269A co-mutation, ALK G1269A was reported to be refractory to 12-month crizotinib … (full text at CIViC) PMID 23434628 · Huang et al., 2013 · Open in CIViC | civic |
| Ensartinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8861In this multicentre phase II study of ALK-positive NSCLC patients that progressed on crizotinib, the safety and efficacy of 225mg daily ensartinib was assessed. Objective responses were seen in 76 (52… (full text at CIViC) PMID 31628085 · Yang et al., 2020 · Open in CIViC | civic |
| ALK G881D + ALK S413N + ALK V597A + ALK Y1239H1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID13125Analysis of 48 lung adenocarcinomas identified novel ALK mutations in six tumours, including S413N in the MAM1 domain, V597A in the MAM2, H694R in an undefined region, G881D in the glycine-rich domain… (full text at CIViC) PMID 21847362 · Wang et al., 2011 · Open in CIViC | civic |
| ALK E1384K + ALK H694R1 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID13124Analysis of 48 lung adenocarcinomas identified novel ALK mutations in six tumours, including S413N in the MAM1 domain, V597A in the MAM2, H694R in an undefined region, G881D in the glycine-rich domain… (full text at CIViC) PMID 21847362 · Wang et al., 2011 · Open in CIViC | civic |
| ALK I117110 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 4 | accepted | EID1283The I1171T mutation in ALK fusions was found in a NSCLC patient shown positive for ALK rearrangement via break apart FISH assay, who progressed after 8 months of crizotinib, and then progressed again … (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | accepted | EID1367A 51 year old female never-smoker was diagnosed with stage IV NSCLC with liver metastases. ALK rearrangement was verified via FISH. She was treated with crizotinib at 250 mg twice daily but discontinu… (full text at CIViC) PMID 25736571 · Ou et al., 2015 · Open in CIViC | civic |
| ALK Inhibitor TAE684 | Lung Non-Small Cell Carcinoma | |||||||
| ALK I1171N + ALK Fusion1 | ||||||||
| Alectinib + CrizotinibSequential | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | accepted | EID1483Case study describes a female (age 58) never-smoker presenting with stage IV NSCLC with an ALK rearrangement (confirmed by fish). Patient was treated with crizotinib (partial response) and alectinib (… (full text at CIViC) PMID 25393796 · Ou et al., 2014 · Open in CIViC | civic |
| ALK I1171T1 | ||||||||
| Ceritinib | Neuroblastoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID9404This case reports a 16-mo-old boy with metastatic neuroblastoma (stage M). Genomic analysis of a diagnostic biopsy of the tumor and matched normal identified two germline mutations in FANCA and somati… (full text at CIViC) PMID 29907598 · Guan et al., 2018 · Open in CIViC | civic |
| ALK L1152P1 | ||||||||
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4613In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1152P co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC | civic |
| ALK L1196Q1 | ||||||||
| Crizotinib | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Resistance | 3 | submitted | EID4609In an in vitro study, cell lines expressing NPM-ALK L1196Q, K299CR06 (endogenous expression) and Ba/F3 (overexpression), demonstrated resistance to crizotinib treatment (IC50: 948 nmol/L and 212 nmol/… (full text at CIViC) PMID 23239810 · Ceccon et al., 2013 · Open in CIViC | civic |
| ALK L1198F2 | ||||||||
| (predisposing) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predisposing | C | Supports Predisposition | 3 | rejected | EID2942In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted t… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | — | submitted | EID4782In a metastatic EML4-ALK rearranged non-small cell lung carcinoma patient harboring ALK C1156Y (a known crizotinib resistance mutation) and ALK L1198F co-mutations, ALK L1198F was associated with rese… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC | civic |
| ALK L1198P1 | ||||||||
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4626In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1198P co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 21948233 · Heuckmann et al., 2011 · Open in CIViC | civic |
| ALK Mutation3 | ||||||||
| (prognostic) | Neuroblastoma | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID13288In a Children's Oncology Group correlative study, 242 pretherapy tumours from patients enrolled on the phase III high-risk neuroblastoma trial ANBL0532 (NCT00567567) underwent ultra-deep targeted sequ… (full text at CIViC) PMID 40036726 · Berko et al., 2025 · Open in CIViC | civic |
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1237In a phase 1 clinical trial (NCT01283516) 130 patients with advanced cancers all harboring ALK alterations were treated with ceritinib. Of 114 NSCLC patients treated with at least 400 mg/daily ceriti… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| Lorlatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | ||||||
| ALK R1192P3 | ||||||||
| (predisposing) | Neuroblastoma | Predisposing | B | Supports Predisposition | 4 | rejected | EID7567A genome-wide scan of single nucleotide polymorphisms in twenty neuroblastoma families identified the ALK gene as being disease linked. Sequencing of ALK exons identified 3 mutations, including R1192P… (full text at CIViC) PMID 18724359 · Mossé et al., 2008 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predisposing | B | Supports Predisposition | 4 | submitted | EID7569A genome-wide scan of single nucleotide polymorphisms in twenty neuroblastoma families identified the ALK gene as being disease linked. Sequencing of ALK exons identified 3 mutations, including R1192P… (full text at CIViC) PMID 18724359 · Mossé et al., 2008 · Open in CIViC | civic |
| Crizotinib | Lung Large Cell Carcinoma | Predictive | D | Supports Resistance | — | submitted | ||
| ALK R1275Q9 | ||||||||
| (predisposing) | Neuroblastoma | Predisposing | B | Supports Predisposition | 5 | submitted | EID7571A genome-wide scan of single nucleotide polymorphisms in twenty neuroblastoma families identified the ALK gene as being disease linked. Sequencing of ALK exons identified 3 mutations, including R1275Q… (full text at CIViC) PMID 18724359 · Mossé et al., 2008 · Open in CIViC | civic |
| ALK Inhibitor TAE684 | Neuroblastoma | Predictive | D | Supports Resistance | 3 | accepted | EID48The SMS-KCNR cell line harboring the R1275Q mutation was resistant to TAE684. PMID 18923525 · George et al., 2008 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID39This study identified previously unknown mutations in the ALK gene in 8% (7/93) of primary neuroblastomas and neuroblastoma cell lines (6/30). R1275Q was found in the germline of one patient sample an… | |
| ALK R214H1 | ||||||||
| Crizotinib | Nasal Type Extranodal NK/T-Cell Lymphoma | Predictive | C | Supports Sensitivity Response | — | submitted | EID4827In a patient with nasal type extranodal NK/T-cell lymphoma harboring ALK R214H mutation, ALK R214H was associated with response to crizotinib monotherapy. Prior to identification of the ALK R214H muta… (full text at CIViC) PMID 27594191 · Thanarajasingam et al., 2016 · Open in CIViC | civic |
| ALK S1206Y + ALK Fusion1 | ||||||||
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID2865In a prospective study (NCT01283516) of 130 cancer patients, a non-small cell lung cancer patient harboring a S1206Y mutation in the ALK portion of the ALK rearrangement was associated with a 60% resp… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| AMER1 R358X1 | ||||||||
| (diagnostic) | Wilms TumorCURATED_BROADER | Diagnostic | B | Supports Positive | 3 | rejected | EID6079This variant was detected in one patient belonging to the Kenyan Wilms Tumor patient cohort from sub-Saharan Africa. PMID 26274016 · Lovvorn et al., 2015 · Open in CIViC | civic |
| RAF1 Fusion1 | ||||||||
| Trametinib | Melanoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID9021In a case report of a patient with metastatic melanoma harhouring an in-frame ANO10-RAF1 fusion, a MEK inhibitor (trametinib) treatment resulted in brief, but significant, tumor regression and symptom… (full text at CIViC) PMID 35135096 · Kim et al., 2018 · Open in CIViC | civic |
| APC Mutation4 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | C | Supports Poor Outcome | 1 | submitted | EID8038While evidence from multiple clinical studies establishing a strong association between loss of function mutations in APC and response to 5-fluorouracil is lacking, some studies suggest APC mutations … (full text at CIViC) PMID 19307944 · Chen et al., 2009 · Open in CIViC | civic |
| G007-LK | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID446G007-LK inhibits in vivo tumor growth in a subset of APC-mutant colorectal cancers xenograft models but may be limited by intestinal toxicity. PMID 23539443 · Lau et al., 2013 · Open in CIViC | civic |
| JW55 | Colon Carcinoma | Predictive | D | Supports | ||||
| NRG1 Fusion + KRAS WildtypeNRG1KRAS1 | ||||||||
| Afatinib | Pancreatic Ductal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7493Whole genome sequencing and transcriptomic analysis were performed on 47 advanced PDAC patients. 3/47 patients were KRAS wildtype and all three of these cases harbored a NRG1 fusion. In a 54-year-old … (full text at CIViC) PMID 31068372 · Jones et al., 2019 · Open in CIViC | civic |
| ARAF Mutation1 | ||||||||
| Cobimetinib | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11297In an open-label, phase II trial, 18 patients with histiocytosis, including two patients with Langerhans cell histiocytosis, of any mutational status were enrolled. Patients received cobimetinib at a … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| ARAF Mutation + ARAF P216A + ARAF S225V1 | ||||||||
| Cobimetinib | Erdheim-Chester Disease | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11296In an open-label, phase II trial, 18 patients with histiocytosis, including 12 patients with Erdheim-Chester disease, one patient with ARAF S225V, and one patient with ARAF P216A, of any mutational st… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
Data updated 19 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Predictive |
| D |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID1285The I1171T ALK kinase domain mutaion was found in the MGH056-1 cell line which was derived from an ALK rearranged NSCLC patient who had progressed on crizotinib and then on alectinib given at lower do… (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC |
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| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1284The MGH056-1 cell line was derived from an NSCLC patient with ALK-rearrangement who had progressed on crizotinib and then on alectinib. the cell line was also resistant to crizotinib and alectinib, an… (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1368A 51 year old female never smoker was diagnosed with stage IV NSCLC with liver metastases, and had adverse response to crizotinib treatment, after which she responded to alectinib until disease progre… (full text at CIViC) PMID 25736571 · Ou et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1344Ba/F3 cells expressing EML4-ALK variant 3 with ALK I1171T mutation were treated with ceritinib, and survival IC50 of 2.6 nM was observed, which compares favorably with highly ceritinib sensitive EML4-… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID4610In a non-small cell lung cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK I1171T co-mutation, ALK I1171T was reported to be refractory to cr… (full text at CIViC) PMID 25393798 · Toyokawa et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1287The MGH056-1 cell line was derived from a patient with ALK rearranged NSCLC who had progressed on crizotinib and then on lower dose alectinib (300 mg twice daily). The I1171T ALK kinase domain mutatio… (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4611In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK I1171T co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Resistance | — | submitted | EID4612In an in vitro study, Karpas299CR cells expressing NPM-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK I1171T co-mutation, demonstrated resistance to crizotinib treatment compared… (full text at CIViC) PMID 24509625 · Zdzalik et al., 2014 · Open in CIViC | civic |
| A |
| Supports Sensitivity Response |
| 4 |
| submitted |
EID11286In this phase II, open-label, single-arm trial, 276 patients with a histologically or cytologically confirmed diagnosis of metastatic non-small-cell lung cancer that carried either an ALK or ROS1 gene… (full text at CIViC) PMID 30413378 · Solomon et al., 2018 · Open in CIViC |
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EID4795In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK R1192P co-mutation, demonstrated resistance to crizotinib treatment (IC50: 421.5 … (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC |
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PMID 18923525 · George et al., 2008 · Open in CIViC
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| Crizotinib | Neuroblastoma | Predictive | B | Supports Sensitivity Response | — | rejected | EID2341Activating mutations in the (ALK) gene are targeted by the dual-specific tyrosine kinase inhibitor crizotinib. The amino acid substitution R1275Q resulted in an improved response to crizotinib. PMID 22072639 · Bresler et al., 2011 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predictive | B | Supports Sensitivity Response | — | submitted | EID2342Activating mutations in the (ALK) gene are targeted by the dual-specific tyrosine kinase inhibitor crizotinib. The amino acid substitution R1275Q resulted in an improved response to crizotinib. The am… (full text at CIViC) PMID 21838707 · Schönherr et al., 2011 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1269This Phase I study of crizotinib involved a cohort of pediatric neuroblastoma patients between ages 12 months and 22 years. In 11 patients with characterized ALK mutations, 4 had R1275Q mutations, and… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1270A cohort of pediatric neuroblastoma patients ages 12 months to 22 years were assessed for response to crizotinib in a Phase I study. 11 patients in this cohort had characterized ALK mutations, 4 of w… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC | civic |
| 〃 | Neuroblastoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID143Cells lines expressing ALK harboring the F1174L mutation are less sensitive to growth inhibition by crizotinib than cells expressing the R1275Q mutation. PMID 22072639 · Bresler et al., 2011 · Open in CIViC | civic |
| Lorlatinib | Neuroblastoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1331In NB-1643 and LAN-5 neuroblastoma cell lines containing R1275Q mutation, PF-06463922 showed 51 and 19 fold greater effect on cell viability over crizotinib treatment respectively. ALK wild-type neuro… (full text at CIViC) PMID 26554404 · Infarinato et al., 2016 · Open in CIViC | civic |
| 3 |
| accepted |
EID445Canonical Wnt signaling in colon carcinoma cells with APC mutation was inhibited by JW55 treatment. PMID 22440753 · Waaler et al., 2012 · Open in CIViC |
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| Regorafenib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID13262In a retrospective analysis of 76 patients with refractory metastatic colorectal cancer treated with regorafenib, APC mutations were detected in approximately 57% of tumors and were significantly asso… (full text at CIViC) PMID 33224274 · Lee et al., 2020 · Open in CIViC | civic |