Cancer Family
Neoplasm
CI-CAN-00000001Explore in graph →
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Cancer Family
CI-CAN-00000001Explore in graph →
Variants & evidence
8,141 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 |
|---|---|---|---|---|---|---|---|---|
| NR4A3 Fusion1 | ||||||||
| (diagnostic) | Acinar Cell CarcinomaALIAS | Diagnostic | C | Supports Positive | 3 | accepted | EID12337In this 2023 study the authors included 4 cases of acinic cell carcinoma of the salivary gland. The age of the patients ranged from 13 to 16 years, and included 2 males and 2 females. Immunohistochemi… (full text at CIViC) PMID 36169793 · Cole et al., 2023 · Open in CIViC | civic |
| NRG1 Fusion4 | ||||||||
| Afatinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID6273In patients with KRAS wild-type (KRASwt) tumors druggable gene fusions have been identified. These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberra… (full text at CIViC) PMID 29802158 · Heining et al., 2018 · Open in CIViC | civic |
| Erlotinib + PertuzumabCombination | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7534In patients with KRAS wild-type (KRASwt) tumors druggable gene fusions have been identified. These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberra… (full text at CIViC) PMID 29802158 · Heining et al., 2018 · Open in CIViC | civic |
| Zenocutuzumab-zbco | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| NTRK1 Fusion12 | ||||||||
| (diagnostic) | NTRK-Rearranged Spindle Cell NeoplasmALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID7293Among pediatric fibroblastic and myofibroblastic proliferating superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, has been variously cla… (full text at CIViC) PMID 27259011 · Agaram et al., 2016 · Open in CIViC | civic |
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11124Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in NTRK fusion-positive solid tumours. 31/54 had objective r… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| 〃 | Solid NeoplasmCURATED_BROADER | |||||||
| NTRK1 F589L + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11542In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 G595R + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 3 | submitted | EID11540In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 G667S + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11543In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 Fusion + NTRK2 Fusion + NTRK3 FusionNTRK1NTRK3NTRK21 | ||||||||
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12071In the STARTRK-NG (NCT02650401) phase 1/2 trial, 43 pediatric and young adult patients (age <22 years) with recurrent or refractory solid tumors, including primary CNS tumors, were evaluated for respo… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC | civic |
| NTRK2 Fusion3 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 3 | submitted | EID7151Genetic alterations in pilocytic astrocytoma (PA) were evaluated. Two new NTRK2 fusion events were identified in this study. These two NTRK2 fusion events, namely QKI-NTRK2 (2 of 96 samples) and NACC2… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 1 | accepted | EID1122254 patients aged 18 or older with metastatic or locally advanced NTRK-fusion positive solid tumours (including ten tumour types and 19 unique histologies) were enrolled in one of three phase 1 or 2 tr… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | ||||||
| NTRK3 Fusion4 | ||||||||
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11125Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in NTRK fusion-positive solid tumours. 31/54 had objective r… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2949in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the a… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| Larotrectinib | Solid NeoplasmCURATED_BROADER | |||||||
| NTRK3 G623R + NTRK3 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 3 | submitted | EID11541In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK3 G696A + NTRK3 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11544In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NUTM1 Fusion4 | ||||||||
| (diagnostic) | NUT CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12050In this 2020 study, the authors included a total of 141 NUT carcinomas defined by rearrangement of NUTM1 detected by IHC, cytogenetics, FISH or sequencing. The median age at diagnosis was 24 years (ra… (full text at CIViC) PMID 32328562 · Chau et al., 2020 · Open in CIViC | civic |
| 〃 | NUT CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12051In this 2004 study, the authors sought to identify carcinomas with translocation t(15;19)(q13, p13.1), which results in the novel oncogenic fusion BRD4::NUTM1 (described as NUT). The authors screened … (full text at CIViC) PMID 15483023 · French et al., 2004 · Open in CIViC | civic |
| 〃 | NUT CarcinomaALIAS | |||||||
| EGFR Fusion1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12551Next generation sequencing was performed on 35023 Chinese cases with 13 different solid tumor types. EGFR Fusions were detected in 106 samples. All EGFR fusions contained the complete tyrosine kinase … (full text at CIViC) PMID 39054543 · Zhang et al., 2024 · Open in CIViC | civic |
| PDGFRA Fusion2 | ||||||||
| (diagnostic) | Chronic Myelomonocytic Leukemia | Diagnostic | A | Supports Negative | 5 | accepted | EID1425The 2016 World Health Organization guidelines for the classification of myeloid malignancies uses the detection of PCM1-JAK2 or rearrangements involving PDGFRA, PDGFRB, or FGFR1 as recommended exclusi… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| 〃 | Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Gene FusionsALIAS | Diagnostic | A | Supports Positive | 5 | accepted | EID1433The 2016 World Health Organization guidelines for the classification of myeloid malignancies and acute leukemia describes a new class of disease defined by myeloid or lymphoid neoplasms associated wit… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| PDGFRB Fusion5 | ||||||||
| (diagnostic) | Chronic Myelomonocytic Leukemia | Diagnostic | A | Supports Negative | 5 | accepted | EID1426The 2016 World Health Organization guidelines for the classification of myeloid malignancies uses the detection of PCM1-JAK2 or rearrangements involving PDGFRA, PDGFRB, or FGFR1 as recommended exclusi… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| 〃 | Hematopoietic and Lymphoid Cell NeoplasmALIAS | Diagnostic | A | Supports Positive | 5 | accepted | EID1434The 2016 World Health Organization guidelines for the classification of myeloid malignancies and acute leukemia describes a new class of disease defined by myeloid or lymphoid neoplasms associated wit… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | ||||||
| NTRK3 e4::e11 | ||||||||
| (oncogenic) | Osteosarcoma | Oncogenic | C | Does Not Support Oncogenicity | 3 | accepted | EID11698Using next-generation DNA and RNA sequencing, three cases harboring NTRK fusions were identified in a cohort of 113 osteosarcomas (including primary tumors and metastases). Each of the three cases had… (full text at CIViC) PMID 32022484 · Ameline et al., 2020 · Open in CIViC | civic |
| NTRK3 e4::e181 | ||||||||
| (oncogenic) | Malignant Colorectal NeoplasmCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID12257The authors describe the creation of a data portal containing over 20,000 gene fusions identified in 9,966 cancer samples and 648 normal samples from The Cancer Genome Atlas. The VPS18-NTRK3 e4::e18 f… (full text at CIViC) PMID 29099951 · Hu et al., 2018 · Open in CIViC | civic |
| VPS37A Underexpression1 | ||||||||
| Cetuximab | Malignant Ovarian Neoplasm | Predictive | D | Supports Resistance | 3 | accepted | EID1981Vps37A-deficient ovarian cancer cells become irresponsive to inhibition by the therapeutic antibody cetuximab in-vitro. PMID 22016507 · Wittinger et al., 2011 · Open in CIViC | civic |
| RET Fusion5 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4850Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had receive… (full text at CIViC) PMID 27544060 · Lin et al., 2016 · Open in CIViC | civic |
| Cabozantinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4847RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with … (full text at CIViC) PMID 27825636 · Drilon et al., 2016 · Open in CIViC | civic |
| Pralsetinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | ||||||
Data updated 15 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 |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID12246On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC) PMID 39908431 · Schram et al., 2025 · Open in CIViC |
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| 〃 | Pancreatic Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID12247On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC) PMID 39908431 · Schram et al., 2025 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID2948The overall safety and antitumor activity of entrectinib was described for two phase I trials of patients with advanced solid tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions. NTRK1 fusions were … (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | rejected | EID29471378 cases of NSCLC were screened. One patient (frequency 0.1%) with a NTRK1 gene rearrangement (SQSTM1-NTRK1 Fusion) was treated with entrectinib in a phase 1 study. The patient had resolution of pri… (full text at CIViC) PMID 26565381 · Farago et al., 2015 · Open in CIViC | civic |
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID6567This was a Phase 1/2 study of 55 patients from 4 months to 76 years old with TRK-fusion positive tumors given NTRK inhibitor Larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall re… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| 〃 | Sarcoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID6569In a Phase 1/2 study involving 15 pediatric patients with infantile fibrosarcoma or soft tissue sarcoma, 8 patients had NTRK1 fusions. The patients were administered Larotrectinib, and 7 out of 8 pati… (full text at CIViC) PMID 29606586 · Laetsch et al., 2018 · Open in CIViC | civic |
| 〃 | Malignant Pancreatic Neoplasm | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7649A patient with pancreatic cancer harboring NTRK fusion was treated with larotrectinib. The best overall response was PR at 2 months but the tumor progressed after 6 months. PMID 31605106 · O'Reilly et al., 2019 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID2953Results from a phase I study show that the TRK inhibitor LOXO-101 is well tolerated and effective, with patients whose tumors bear NTRK fusions responding well and durably to this targeted therapy. Th… (full text at CIViC) PMID 26603524 · 2016 · Open in CIViC | civic |
| 〃 | Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | rejected | EID2956LOXO-101 is an orally administered inhibitor of the TRK kinase and is highly selective only for the TRK family of receptors. The tumor of a 41-year-old woman with soft-tissue sarcoma metastatic to the… (full text at CIViC) PMID 26216294 · Doebele et al., 2015 · Open in CIViC | civic |
| 〃 | Malignant Pancreatic Neoplasm | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID6051In a Phase I/II study of Larotrectinib, highly selective TRK inhibitor, one patient with pancreatic cancer with NTRK fusion showed PR. PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| 〃 | Cholangiocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID6052In a Phase I/II study of Larotrectinib, highly selective TRK inhibitor, two patient with cholangiocarcinoma with NTRK fusion was enrolled. One of the two patient showed PR. PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| Crizotinib + Larotrectinib + LestaurtinibSubstitutes | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1019Two patients were found to harbor gene fusions maintaining the kinase domain of NTRK1 (3' partner), specifically: MPRIP-NTRK1 and CD74-NTRK1. Both of these fusions lead to constitutive kinase activit… (full text at CIViC) PMID 24162815 · Vaishnavi et al., 2013 · Open in CIViC | civic |
| Supports Sensitivity Response |
| 2 |
| accepted |
EID10392A pooled analysis of three phase 1/2 clinical trials investigating the efficacy and safety of larotrectinib in 159 NTRK fusion positive solid tumor patients (1 month - 84 years old) confirmed larotrec… (full text at CIViC) PMID 32105622 · Hong et al., 2020 · Open in CIViC |
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| Predictive |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID6568This was a Phase 1/2 study of 55 patients from 4 months to 76 years old with TRK-fusion positive tumors given NTRK inhibitor Larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall re… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC |
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| 〃 | Malignant NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID2954Results from a phase I study show that the TRK inhibitor LOXO-101 is well tolerated and effective, with patients whose tumors bear NTRK fusions responding well and durably to this targeted therapy. PMID 26603524 · 2016 · Open in CIViC | civic |
| C |
| Supports Positive |
| 2 |
| accepted |
EID12009RNA sequencing identified NUTM1 fusions in six patients with primary undifferentiated soft tissue and visceral tumors. Fusions included BRD4::NUTM1 (three cases), BRD3::NUTM1, MXD1::NUTM1, and BCORL1… (full text at CIViC) PMID 29356724 · Dickson et al., 2018 · Open in CIViC |
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| Molibresib | NUT CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12055NUT carcinoma is known to be driven by BET fusion proteins, including BRD4::NUTM1 and BRD3::NUTM1, raising the possibility of response to BET inhibitors. Of 19 patients with NUT carcinoma treated wit… (full text at CIViC) PMID 32328561 · Piha-Paul et al., 2020 · Open in CIViC | civic |
| Supports Positive |
| 4 |
| submitted |
EID7022This study showed that, when detected in the context of B-cell lymphoblastic leukemia/lymphoma (B-ALL), PDGFRB fusions with different partner genes are associated with Ph-like molecular subtype of B-A… (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC |
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| Imatinib | Myeloproliferative NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1498Twelve patients with BCR-ABL-negative chronic myeloproliferative disease and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had p… (full text at CIViC) PMID 16960151 · David et al., 2007 · Open in CIViC | civic |
| 〃 | Myeloproliferative NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11272In this phase II, open-label, single-arm trial, 106 patients with 40 different malignancies were enrolled (78.5% solid tumours, 21.5% hematologic malignancies), including seven with myeloproliferative… (full text at CIViC) PMID 18451237 · Heinrich et al., 2008 · Open in CIViC | civic |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID11233In an open-label, phase 1/2 trial on 87 patients with NSCLC including RET-fusion were given 400 mg once-daily oral pralsetinib, with the outcome measured as overall response rate. Overall responses we… (full text at CIViC) PMID 34118197 · Gainor et al., 2021 · Open in CIViC |
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| 〃 | Malignant Thyroid Gland Neoplasm | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID11234In a phase 1/2, open-label trial, 122 patients with RET-mutant medullary cancer and 20 with RET-fusion positive thyroid cancer were administered 400 mg daily oral pralsetinib. The overall response rat… (full text at CIViC) PMID 34118198 · Subbiah et al., 2021 · Open in CIViC | civic |
| 〃 | Solid NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID11266In the phase 1/2 clinical trial NCT03037385, one arm assessed the therapeutic benefit of the selective RET inhibitor pralsetinib across a range RET fusion positive solid tumors, excluding NSCLC and th… (full text at CIViC) PMID 35962206 · Subbiah et al., 2022 · Open in CIViC | civic |