Cancer Family
Respiratory System Neoplasm
CI-CAN-00000049Explore in graph →
Non-malignant2,727 active trials51 approved drugs619 evidence items
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Cancer Family
CI-CAN-00000049Explore in graph →
Variants & evidence
1,284 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 |
|---|---|---|---|---|---|---|---|---|
| KRAS KRAS4A underexpression1 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9600In a clinical study including 148 patients expressing KRAS mutants, low expression of KRAS4A is significantly associated with decreased OS (p = 2.72 x 10^-3) and low proportion of KRAS4A is also signi… (full text at CIViC) PMID 29504894 · Yang et al., 2018 · Open in CIViC | civic |
| KRAS Mutation22 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1700In a study of 1036 patients with lung adenocarcinoma, patients with KRAS mutations (n=241) showed worse prognosis (OS: 19 months versus 23 months; HR=1.21; P=0.048). PMID 22810899 · Johnson et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID3715Analysis was performed on the placebo group (n=451) of the Phase III study SATURN using erlotinib maintenance therapy for patients with advanced NSCLC who were selected for response or stable disease … (full text at CIViC) PMID 21969500 · Brugger et al., 2011 · Open in CIViC | civic |
| Abemaciclib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | |||||
| KRAS Q61H1 | ||||||||
| Vemurafenib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID3865In an in vitro study, the H460C cell line expressing a KRAS Q61H mutation was associated with resistance to vemurafenib treatment. Resistance was determined by assessing cell viability and phosphoryla… (full text at CIViC) PMID 25706985 · Joshi et al., 2015 · Open in CIViC | civic |
| KRAS Wildtype1 | ||||||||
| Cetuximab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID11659In a clinical study of 49 patients, 10 patients with Non-Small Cell Lung Cancer (NSCLC) and wild-type KRAS gene were treated with Cetuximab. After 16 weeks, no clinical activity was observed. A PFS of… (full text at CIViC) PMID 33090333 · Fisher et al., 2020 · Open in CIViC | civic |
| LRP1B Loss-of-function1 | ||||||||
| Immune Checkpoint Inhibitor | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID12652In a retrospective LUAD cohort treated with PD-1 plus CTLA-4 blockade (n = 59; LRP1B-MT n = 15, LRP1B-WT n = 44), LRP1B-mutated tumors showed significantly longer PFS (log-rank p = 0.0016), along with… (full text at CIViC) PMID 37057124 · He et al., 2023 · Open in CIViC | civic |
| NTRK1 Fusion2 | ||||||||
| (oncogenic) | Lung Squamous Cell Carcinoma | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID13048A retrospective study of tumors sequenced through the Veterans Health Administration National Precision Oncology Program identified NTRK rearrangements in 25 of 22,450 solid tumors. Twelve patients wi… (full text at CIViC) PMID 36926986 · Zhou et al., 2023 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID13058Xu et al. retrospectively analyzed paired pre- and post-EGFR tyrosine kinase inhibitor samples from 3,873 patients with EGFR-mutant lung adenocarcinoma and identified an acquired LRRC71::NTRK1 fusion … (full text at CIViC) PMID 31372039 · Xu et al., 2019 · Open in CIViC | civic |
| MAP2K1 K57N2 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID2935In a study of 6,024 lung adenocarcinomas, 36 conferred MEK1 mutations whereby 64% (n=23) were K57N and 19% (n=7) were Q56P. Median overall survival of MEK1-mutated tumors was not significantly differe… (full text at CIViC) PMID 25351745 · Arcila et al., 2015 · Open in CIViC | civic |
| Selumetinib | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID2936Mutational profiling of 207 lung adenocarcinomas identified in 2 of with activating mutation in exon 2 of MEK1 (K57N) in the nonkinase portion of the kinase. Neither of these two tumors harbored known… (full text at CIViC) PMID 18632602 · Marks et al., 2008 · Open in CIViC | civic |
| MAP2K7 E116K1 | ||||||||
| (prognostic) | Malignant Lung Neoplasm | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID1420Study examined rare SNPs on MAP2K7 among a discovery and two validation cohorts. It was discovered that the E116K genotype was associated with a reduced median survival time of 4 and 7 months for E/K … (full text at CIViC) PMID 27028764 · Qiu et al., 2016 · Open in CIViC | civic |
| MAPK1 Amplification1 | ||||||||
| WZ4002 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | accepted | EID792Resistance to WZ4002 was induced in cell lines. Amplification of MAPK1 or downregulation of ERK-pathway inhibitors led to resistance to EGFR inhibition with WZ4002. Chemical inhibition (MEK inhibition… (full text at CIViC) PMID 22961667 · Ercan et al., 2012 · Open in CIViC | civic |
| MDM2 Amplification + MET D1010HMDM2MET1 | ||||||||
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11374A 76-year old female (former light smoker) diagnosed with metastatic squamous lung carcinoma was found to have MET D1010H and MDM2 mutation following mutation analysis. She was originally treated with… (full text at CIViC) PMID 25898965 · Mendenhall et al., 2015 · Open in CIViC | civic |
| MET Amplification12 | ||||||||
| Capmatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8849In a phase 2 trial, a total of 364 patients with non-small cell lung cancer and MET alterations received the MET inhibitor Capmatinib after assignment to cohorts based on prior treatment and type of M… (full text at CIViC) PMID 32877583 · Wolf et al., 2020 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7502In a phase II trial patients with NSCLC harboring with MET amplification or MET exon 14 mutations were treated with multikinase inhibitor crizotinib. MET amplification was defined as MET/CEP7 ration >… (full text at CIViC) PMID 31416808 · Landi et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
| MET Amplification + MET Exon 14 Skipping Mutation1 | ||||||||
| Crizotinib | Lung Sarcomatoid Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11375A 74-year-old woman with stage II Pulmonary Sarcomatoid Carcinoma (PSC) was treated with neoadjuvant platinum/taxane chemotherapy with no improvement. Chemotherapy was stopped due to resistance and po… (full text at CIViC) PMID 26215952 · Liu et al., 2016 · Open in CIViC | civic |
| MET Amplification + MET Splice Site (c.2888_2919del)1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID11462A 76-year old male (non-smoker) presented with stage IV lung adenocarcinoma with metastatic disease in the lung and thoracic vertebra (T2). Next-generation sequencing revealed a MET exon 14 skipping m… (full text at CIViC) PMID 27257131 · Liu et al., 2016 · Open in CIViC | civic |
| MET Amplification + MET Splice Site (c.3028G>A)1 | ||||||||
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID109564-year old female (non-smoker) was diagnosed with NSCLC. A c.3028 G->A mutation was identified in exon 14 resulting in exon 14 skipping. Further, amplification of the MET gene was observed. The patie… (full text at CIViC) PMID 26729443 · Awad et al., 2016 · Open in CIViC | civic |
| MET Amplification + MYC AmplificationMETMYC2 | ||||||||
| Capmatinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 3 | submitted | EID11420An 82-year old male (smoker: 60 pack-years) was diagnosed with lung adenocarcinoma. Initial tumor tissue testing revealed MET amplification (GCN = 13.5). The patient was enrolled in a phase 2 trial an… (full text at CIViC) PMID 36248327 · Choi et al., 2022 · Open in CIViC | civic |
| Capmatinib + ICX-101Sequential | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11421A patient diagnosed with lung adenocarcinoma had cells cultured to create patient-derived cell lines. Such cells exhibited MET amplification and showed overexpression of MYC. Capmatinib was administer… (full text at CIViC) PMID 36248327 · Choi et al., 2022 · Open in CIViC | civic |
Data updated 8 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.
| Supports Sensitivity Response |
| 3 |
| accepted |
EID4842In this multicenter phase I study of abemaciclib, a total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Radiographic responses were achieved in previously tre… (full text at CIViC) PMID 27217383 · Patnaik et al., 2016 · Open in CIViC |
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| Afatinib + TrametinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID992An shDNA screen identified synergy between ERBB3 Inhibition and MEK Inhibition in KRAS mutated cell lines. Dual EGFR/ERBB2 Inhibitors afatinib and dacomitinib and MEK Inhibition was synergistic in col… (full text at CIViC) PMID 24685132 · Sun et al., 2014 · Open in CIViC | civic |
| B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID989SiRNA Screening in 37 KRAS Mutant colorectal cancer cell lines identified RAF1 and MEK Inhibition as synergistic, whereas MEK Inhibition alone led to quick resistance via upregulation of RAF-signallin… (full text at CIViC) PMID 25199829 · Lamba et al., 2014 · Open in CIViC | civic |
| Docetaxel | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID4997Of the 275 patients assessable for KRAS mutation status, 49 (18%) were positive for KRAS mutation. There were no differences between treatments in OS, PFS, or response rates according to KRAS mutation… (full text at CIViC) PMID 20038723 · Douillard et al., 2010 · Open in CIViC | civic |
| Docetaxel + ErlotinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID4996222 EGFR-wt patients with advanced NSCLC were randomized to receive docetaxel or erlotinib In this study (4 patients not eligible, leaving 109 in each arm). KRAS was mutated in 25 and 26 out of 109 pa… (full text at CIViC) PMID 26209642 · Rulli et al., 2015 · Open in CIViC | civic |
| Docetaxel + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Resistance | 5 | accepted | EID2998A phase 3 study of selumetinib and docetaxel in KRAS mutant, previously treated NSCLC. 866 were enrolled and 510 randomized. Median progression-free survival was 3.9 months with selumetinib + docetaxe… (full text at CIViC) PMID 28492898 · Jänne et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID99987 patients with KRAS mutant stage IIB-IV NSCLC after first line therapy were randomly assigned (1:1) to oral selumetunib and docetaxel or docetaxel and Placebo. Median OS was 9·4 months (6·8-13·6) in… (full text at CIViC) PMID 23200175 · Jänne et al., 2013 · Open in CIViC | civic |
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID3895In the placebo-controlled Phase III study SATURN, using erlotinib maintenance therapy for patients with advanced NSCLC who were selected for response or stable disease after first line chemotherapy, K… (full text at CIViC) PMID 21969500 · Brugger et al., 2011 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 2 | accepted | EID2242In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib and placebo, patients whose tumors harbored KRAS mutations (n=8) had a lower 12-week progression-free survival… (full text at CIViC) PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC | civic |
| Erlotinib + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID486838 KRAS wild-type patients were randomized to erlotinib or combination of selumetinib with erlotinib. 41 KRAS mutant patients were randomized to selumetinib or the combination. The primary end points … (full text at CIViC) PMID 26802155 · Carter et al., 2016 · Open in CIViC | civic |
| Erlotinib + TeprotumumabCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID3713In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib daily and teprotumumab (R1507) weekly or every three weeks, patients whose tumors harbored KRAS mutations had … (full text at CIViC) PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC | civic |
| Erlotinib + GefitinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID2385In a retrospective study, 166 non-small cell lung cancer (NSCLC) patients that tended to have selected characteristics known to be predictive for TKI sensitivity (i.e. women, never smokers, and patien… (full text at CIViC) PMID 21258250 · Ludovini et al., 2011 · Open in CIViC | civic |
| Immune Checkpoint Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | E | Supports Sensitivity Response | 2 | accepted | EID4864This meta-analysis of 5 studies with 752 non-small cell lung cancer patients examined the association between PD-L1 expression and KRAS mutation status. KRAS-mutant tumors were marginally more likely … (full text at CIViC) PMID 28259530 · Li et al., 2017 · Open in CIViC | civic |
| MEK Inhibitor RO4987655 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Resistance | 3 | accepted | EID997This was a phase I expansion and pharmacodynamic study of oral MEK inhibitor RO4987655 on advanced cancer. Of 18 patients with KRAS mutant non-small cell lung cancer (NSCLC), 10 experienced clinical b… (full text at CIViC) PMID 24947927 · Zimmer et al., 2014 · Open in CIViC | civic |
| Atezolizumab + NivolumabSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4863A meta-analysis of randomized trials to investigate if KRAS mutation status affects survival benefits of immune checkpoint inhibition (ICI) in patients with advanced NSCLC. Of 3 eligible studies using… (full text at CIViC) PMID 28525386 · Kim et al., 2017 · Open in CIViC | civic |
| Pembrolizumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4865In this study we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 … (full text at CIViC) PMID 28451792 · Chen et al., 2017 · Open in CIViC | civic |
| Salirasib | Lung Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID1218In a study of 30 lung adenocarcinoma patients with documented KRAS mutations, farnesylthiosalicylic acid (Salirasib) mono-therapy resulted in no partial responses and did not improve overall survival … (full text at CIViC) PMID 21847063 · Riely et al., 2011 · Open in CIViC | civic |
| Trametinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID4867In this phase II trial, trametinib or docetaxel was given to patients with advanced KRAS-mutant NSCLC. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (HR 1.14; p = 0.5… (full text at CIViC) PMID 25722381 · Blumenschein et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1220In a phase 1 clinical trial for the use of trametinib for various advanced solid tumors, 22 out of 30 NSCLC patients harbored KRAS mutations. Of those 22 patients with mutant KRAS, 8 saw reductions in… (full text at CIViC) PMID 22805291 · Infante et al., 2012 · Open in CIViC | civic |
| Docetaxel + Pemetrexed + TrametinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4862This phase I/Ib two-part study evaluated trametinib in combination with anticancer agents docetaxel or pemetrexed in NSCLC with and without KRAS mutations. Confirmed partial response (PR) was observed… (full text at CIViC) PMID 27876675 · Gandara et al., 2017 · Open in CIViC | civic |
| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID7639Patients with non-small cell lung carcinoma harboring MET alterations were treated with crizotinib. MET amplification was defined as more than or equal to 6 copies. The response rate at 2 cycles in pa… (full text at CIViC) PMID 31584608 · Moro-Sibilot et al., 2019 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID735A case-study of an ALK-negative patient with MET amplification (MET/CEP7 ratio >5.0) who achieved a durable partial response to MET/ALK-inhibitor crizotinib. PMID 21623265 · Ou et al., 2011 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1692In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an MET-Amplification was identified using CGP. The patient attained a reduction in the target lesions by 38.7%, and the pa… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11383A 72-year old woman (former smoker: 12 pack-years) with advanced lung adenocarcinoma received 250 mg of crizotinib twice daily after first line chemotherapy with carboplatin, pemetrexed, and maintenan… (full text at CIViC) PMID 26791794 · Jorge et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID836Case report of a patient with MET amplification without high-level MET/CEP7 ratio, MET exon 14 mutation or overexpression who achieved rapid response to crizotinib. PMID 26724472 · Zhang et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Squamous Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID890Case report of a 73 year old patient with advanced squamous cell carcinoma of the lung that tested negative for EGFR, KRAS and PIK3CA mutations and ALK and ROS1 rearrangements. c-MET amplification was… (full text at CIViC) PMID 24192513 · Schwab et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1713Case report of two patients with MET amplification (MET:CEP7 ratio ≥5) and no concomitant MET exon 14 deletion. A response to crizotinib was observed in both cases suggesting that MET amplification ma… (full text at CIViC) PMID 27664533 · Caparica et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID15662 MET amplified NSCLC cell lines (EBC-1 and H1993), as well as 2 EGFR mutant and 2 MET and EGFR wild type cell lines were treated with ALK and MET inhibitor crizotinib, and the MET amplified cells had… (full text at CIViC) PMID 21716144 · Tanizaki et al., 2011 · Open in CIViC | civic |
| Gefitinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | accepted | EID733In this study a gefitinib-sensitive cell-line (HCC827), acquired gefitinib resistance (HCC827 GR) by a focal amplification of MET. Resistance was conferred by the MET amplification driving ERBB3 (HER… (full text at CIViC) PMID 17463250 · Engelman et al., 2007 · Open in CIViC | civic |
| Erlotinib + GefitinibSubstitutes | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 2 | accepted | EID1392155 patients with lung adenocarcinomas underwent rebiopsy and genotyping (EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS, PIK3CA and FISH for MET and HER2) after the development of acquired resistance to E… (full text at CIViC) PMID 23470965 · Yu et al., 2013 · Open in CIViC | civic |