Cancer
Neoplasm of Uncertain Histogenesis
CI-CAN-00000034Explore in graph →
Non-malignant20,280 active trials259 approved drugs3,813 evidence items
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Cancer
CI-CAN-00000034Explore in graph →
Variants & evidence
7,620 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 |
|---|---|---|---|---|---|---|---|---|
| UCK2 Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13316shRNA-mediated reduction of UCK2 expression significantly sensitized HCT-116, HT-29, and SW620 colorectal cancer cells to fluorouracil, decreasing IC50 approximately 3- to 6-fold. PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| NTRK2 e6::e71 | ||||||||
| (oncogenic) | Osteosarcoma | Oncogenic | C | Does Not Support Oncogenicity | 3 | accepted | EID11697Using next-generation DNA and RNA sequencing, three cases harboring NTRK fusions were identified in a cohort of 113 osteosarcomas (including both primary tumors and metastases). Each of the three case… (full text at CIViC) PMID 32022484 · Ameline et al., 2020 · Open in CIViC | civic |
| UGT1A1 UGT1A1*281 | ||||||||
| Belinostat | Malignant NeoplasmALIAS | Predictive | A | Supports Adverse Response | 5 | accepted | EID1792The FDA approved package insert for Belinostat recommends dose adjustment for UGT1A1*28 allele homozygotes. PMID 26313268 · Goey et al., 2016 · Open in CIViC | civic |
| UGT1A1 UGT1A1*601 | ||||||||
| Belinostat | Malignant NeoplasmALIAS | Predictive | B | Supports Adverse Response | 4 | accepted | EID1795In a phase 1 trial belinostat (400-800mg/m2/24h) was administered to 25 patients in combination with cisplatin and etoposide. Endpoints were associations between genotype of UGT1A1 and pharmacokinetic… (full text at CIViC) PMID 26313268 · Goey et al., 2016 · Open in CIViC | civic |
| UGT1A Overexpression1 | ||||||||
| Ganetespib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID866Colorectal cancer cell lines were evaluated for response to the HSP90 inhibitor ganetespib. Correlating cell line-specific IC50s with the corresponding gene expression patterns revealed a possible re… (full text at CIViC) PMID 25210794 · Landmann et al., 2014 · Open in CIViC | civic |
| UMPS Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID13322shRNA-mediated reduction of UMPS expression increased resistance to fluorouracil by approximately twofold in HCT-116 and SW620 colorectal cancer cells, as measured by increased IC50. PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| UNG Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13319Reduction of UNG expression by shRNA significantly sensitized all three colorectal cancer cell lines to fluorouracil. Across the UNG, NME1, and RRM1 experiments, IC50 decreases ranged from approximate… (full text at CIViC) PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| JAK2 Fusion1 | ||||||||
| (diagnostic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 3 | accepted | EID7705In B-lymphoblastic leukemia/lymphoma (B-ALL), the presence of this fusion is associated with so-called BCR/ABL1 like (Ph-like) subtype of the disease. The USP25-JAK2 fusion is rare; this study involve… (full text at CIViC) PMID 28408464 · Reshmi et al., 2017 · Open in CIViC | civic |
| USP7 mutation1 | ||||||||
| (oncogenic) | Burkitt Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11824Described in multiple genome-wide studies of BL PMID 30617194 · Grande et al., 2019 · Open in CIViC | civic |
| ABL1 Fusion1 | ||||||||
| (oncogenic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Oncogenic | A | Supports Oncogenicity | 4 | submitted | EID6936The study showed association of the ABL1 fusions with partner genes other than BCR with a specific molecular/genetic subtype of B-lymphoblastic leukemia characterized by the expression signature simil… (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC | civic |
| ABL2 Fusion2 | ||||||||
| (diagnostic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | A | Supports Positive | 3 | submitted | EID6963The study showed that in B-ALL the the presence of ABL2 fusions with different partner genes is diagnostic for the so-called BCR-ABL1-like (or Philadelphia (Ph)-like) molecular subtype of B-ALL. Ph-l… (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC | civic |
| Imatinib | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7250The RCSD1-ABL2 fusion was identified in a 5 yo boy with Ph-like B-ALL and Klinefelter syndrome. Following standard induction therapy the patient had an MRD of 1.2% in bone marrow, and continued to be … (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC | civic |
| ALK Fusion38 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1282In this Phase II trial of 87 patients (NCT01871805), alectinib was assayed for safety and efficacy in ALK positive NSCLC that had progressed on crizotinib. Of 69 patients with measurable disease, 35 a… (full text at CIViC) PMID 26708155 · Shaw et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7284In a phase 3 trial, 303 patients with NSCLC with ALK fusion were randomly assigned to alectinib arm (N=152) or crizotinib arm (N=151). PFS was significantly longer with alectinib than with crizotinib … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
Data updated 16 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 |
| 5 |
| submitted |
EID7533In this phase II study the safety, efficacy, and pharmacokinetics of twice daily 600mg alectinib treatment was assessed in 138 patients with advanced NSCLC harboring ALK rearrangements (previously det… (full text at CIViC) PMID 26598747 · Ou et al., 2016 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID7872National Comprehensive Cancer Network (NCCN) guidelines recommend alectinib for advanced ALK-positive NSCLC who are previously untreated or previously treated with crizotinib, including those with bra… (full text at CIViC) PMID 30030733 · Paik et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID8657A randomized phase 3 trial (J-ALEX) of 207 Japanese ALK-positive NSCLC patients compared the efficacy and safety of alectinib (300mg twice daily) and crizotinib (250mg twice daily) in the first-line s… (full text at CIViC) PMID 28501140 · Hida et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID12012In this global phase 3 trial, 257 patients with ALK-positive Non-Small-Cell Lung Cancer were treated with either alectinib (n = 130) or chemotherapy (n = 127). 93.8 % of the patients who had received … (full text at CIViC) PMID 38598794 · Wu et al., 2024 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1279In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in treating locally advanced or metastatic ALK-positive NSCLC that had progressed or been resistant to … (full text at CIViC) PMID 25153538 · Gadgeel et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1272In this initial report of a single-arm Phase I and II study (JapicCTI-101264) of alectinib (CH5424802), 46 patients with advanced or metastatic ALK-rearranged non small cell lung cancer (NSCLC) were a… (full text at CIViC) PMID 23639470 · Seto et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1273In this case study of a critically ill 29 year old male nonsmoker with advanced metastatic ALK-positive NSCLC, alectinib (CH5424802), was administered as first line treatment. Where most clinical tria… (full text at CIViC) PMID 26938871 · Yoshida et al., 2016 · Open in CIViC | civic |
| Brigatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11121The phase III ALTA-1L open-label randomized trial examined 275 NSCLC patients given brigatinib (137 patients) vs crizotinib (138 patients). Patients were ALK fusion positive by an FDA-approved diagno… (full text at CIViC) PMID 32780660 · Camidge et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | rejected | EID1323Development of second generation ALK inhibitors has been underway in order to address resistance to first line treatments such as crizotinib in ALK-rearranged NSCLC. Brigatinib is a potent dual inhib… (full text at CIViC) PMID 26951079 · Wu et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID4835In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-pos. NSCLC. They were randomly assigned (1:1) to oral Brigatinib 90 mg once daily (arm A) or 180 mg … (full text at CIViC) PMID 28475456 · Kim et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7053A single-arm, open-label, phase 1/2 trial showed that 51 (72% [60-82]) out of 71 patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC responded to the ALK inhibitor, Brigatinib. PMID 27836716 · Gettinger et al., 2016 · Open in CIViC | civic |
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7285In a phase 3 trial, patients with previously treatmented NSCLC with ALK fusion were randomly assigned to ceritinib or chemotherapy. Ceritinib showed a significant improvement in median PFS compared w… (full text at CIViC) PMID 28602779 · Shaw et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11190In a phase 3 trial (ASCEND-4, NCT01828099), a comparison of the selective ALK inhibitor ceritinib (750 mg daily) to chemotherapy (cisplatin or carboplatin plus pemetrexed) in 376 untreated ALK-fusion… (full text at CIViC) PMID 28126333 · Soria et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1175Updated results from ASCEND-1 trial assessing safety and activity of ceritinib in ALK rearranged locally advanced or metastatic NSCLC. 255 patients were enrolled and received at least one dose of ceri… (full text at CIViC) PMID 26973324 · Kim et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID7535This dose escalation phase 1 study examined the safety and efficacy of ceritinib in 122 NSCLC patients harboring ALK rearrangements (determined by break-apart FISH). Maximum tolerated dose (MTD) was d… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7546In a phase I study of the efficacy of ceritinib in ALK fusion positive cancer, a single patient with anaplastic large cell lymphoma was treated with 750mg daily ceritinb and had a partial response. Du… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1187In the Phase I study PROFILE 1001 (NCT00585195), a recommended crizotinib dose of 250 mg twice daily for 28 day cycles was established. Among 1,500 advanced NSCLC patients who were screened for ALK-re… (full text at CIViC) PMID 20979469 · Kwak et al., 2010 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1198This two arm Phase III study named PROFILE 1007 (NCT00932893) was performed to assess crizotinib vs. established chemotherapy in non-small cell lung cancer patients positive for ALK rearrangement (ass… (full text at CIViC) PMID 23724913 · Shaw et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1199This phase 3 trial named PROFILE 1014 (NCT01154140) compared crizotinib to established chemotherapy in first-line treatment for this disease. The study consisted of 343 patients with advanced or metas… (full text at CIViC) PMID 25470694 · Solomon et al., 2014 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID11218This trial enrolled 26 patients with anaplastic large cell lymphoma (ALCL). The groups received twice daily crizotinib at doses of either 165 or 280 mg/m2. 83% of the 165 mg/m2 ALCL patients had a com… (full text at CIViC) PMID 28787259 · Mossé et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1200This retrospective study of patients from the PROFILE 1001 and 1005 studies of crizotinib in advanced ALK-rearranged NSCLC assessed the potential benefit of crizotinib beyond progressive disease (CBPD… (full text at CIViC) PMID 24478318 · Ou et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1201This prospective Phase III study named Profile 1014 on NSCLC ALK-rearranged patients assessed intracranial disease control rate (IC-DCR) in the subset of patients entering the study with preexisting t… (full text at CIViC) PMID 27022118 · Solomon et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1419In a retrospective study comparing survival outcomes in a subgroup of 82 ALK-positive crizotinib-treated patients enrolled in a phase 1 clinical trial (NCT00585195), crizotinib therapy was associated … (full text at CIViC) PMID 21933749 · Shaw et al., 2011 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1577A phase-3 clinical trial evaluated 347 patients with ALK-positive lung cancer. The study compared crizotinib treatment (n=173) with chemotherapy treatment of either pemetrexed or docetaxel (n=174). … (full text at CIViC) PMID 26466010 · 2015 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID7361In this phase I/II study, 26 patients with relapsed/refractory ALK-positive ALCL were administered crizotinib orally twice daily in 28-day cycles as a single agent for an indefinite duration. Patients… (full text at CIViC) PMID 28787259 · Mossé et al., 2017 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID1140417 patients with ALK-positive advanced anaplastic large‐cell lymphoma (ALCL) enrolled in the PROFILE 1013 (NCT01121588) phase 1b single-arm, open-label, multi-centre study received crizotinib. ORR was… (full text at CIViC) PMID 29352732 · Gambacorti-Passerini et al., 2018 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1240Crizotinib at 250mg daily was given to two patients with relapsed ALK-rearranged anaplastic large cell lymphoma (ALCL). Patient one, 26 yrs old, had been treated with the CHOP-15 chemotherapy regimen,… (full text at CIViC) PMID 21345110 · Gambacorti-Passerini et al., 2011 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | C | Supports Sensitivity Response | 3 | rejected | EID1242Four adult ALK-rearranged anaplastic large cell lymphoma (ALCL) patients were resistant to chemotherapy after 3 or more lines of treatment. The patients were administered 250 mg crizotinib twice dail… (full text at CIViC) PMID 23006951 · Foyil et al., 2012 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1691In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an EML4-ALK-E13;A20 rearrangement was identified using CGP. The patient attained a reduction in the target lesions by 14.2… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC | civic |
| 〃 | Thyroid Gland Anaplastic CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID5954A patient with anaplastic thyroid carcinoma harboring ALK rearrangement received crizotinib after chemotherapy for pulmonary recurrence. Crizotinib showed confirmed response of more than 90% by tumor … (full text at CIViC) PMID 24687827 · Godbert et al., 2015 · Open in CIViC | civic |
| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1264A 27 year old female patient with advanced-stage IV, CD20 negative diffuse large B cell lymphoma (DLBCL). ALK rearrangement was determined by FISH, but the ALK fusion partner was not determined due to… (full text at CIViC) PMID 24330038 · Wass et al., 2014 · Open in CIViC | civic |
| 〃 | Vaginal SarcomaALIAS | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID6042Patient was 34-year-old woman with vaginal sarcoma, which was excised with positive surgical margins. Fluorescence in situ hybridization testing of her tumor revealed anaplastic lymphoma kinase gene … (full text at CIViC) PMID 26942346 · Forde et al., 2016 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID7144Authors report the ALK inactivation in ALK-positive ALCL induces an increase in BCL2 levels, which could contribute to therapeutic failures of current ALK targeted therapies. Their data strongly sugge… (full text at CIViC) PMID 30679328 · Torossian et al., 2019 · Open in CIViC | civic |
| 〃 | Colorectal Adenocarcinoma | Predictive | E | Supports Sensitivity Response | 1 | accepted | EID133426 colorectal adenocarcinoma samples were run on Affymetrix human Exon 1.0 arrays and a computational method that assessed differential 5' and 3' gene expression for each gene was used to find potenti… (full text at CIViC) PMID 19737969 · Lin et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | E | Supports Sensitivity Response | 1 | accepted | EID133584 breast cancer samples acquired from commercial sources were assayed on Affymetrix human exon 1.0 arrays. A computational method was used to find potential gene fusions which assessed differential e… (full text at CIViC) PMID 19737969 · Lin et al., 2009 · Open in CIViC | civic |
| Alectinib + CrizotinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID4858In a randomized, open-label phase 3 trial 303 patients with ALK-positive, previously untreated NSCLC (including asympt. CNS disease) were randomized to reiceive either Alectinib or Crizotinib. During … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC | civic |