Histology
Non-Small Cell Carcinoma
CI-CAN-00001292Explore in graph →
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- C65151
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Histology
CI-CAN-00001292Explore in graph →
Variants & evidence
1,206 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 G12C14 | ||||||||
| Pan-RAF/MEK Molecular Glue NST-628 + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13158In KRAS G12C-mutant NCI-H23 tumor models, NST-628 enhanced the activity of KRAS G12C inhibition. In vivo, NST-628 at 2 mg/kg once daily or sotorasib at 100 mg/kg once daily slowed NCI-H23 tumor growth… (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC | civic |
| Sotorasib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID9431The phase II cohort of the CodeBreaK 100 study (NCT03600883) investigated the activity of the KRAS G12C inhibitor sotorasib in previously treated patients with KRAS G12C-mutated non-small cell lung ca… (full text at CIViC) PMID 34096690 · Skoulidis et al., 2021 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7387In a phase I trial, patients with solid tumor harboring KRAS G12C mutation were enrolled. Five out of ten patients with NSCLC showed partial response in this study. PMID 31239544 · Lindsay et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7455In a phase1 trial, patients with advanced solid tumor harboring KRAS G12C mutation were treated selective KRAS G12C inhibitor AMG 510. Among the 10 patients with non-small cell lung carcinoma, 4 patie… (full text at CIViC) | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID9959In a dose escalation study (NCT03600883) of AMG 510 (sotorasib) treatment, four KRAS G12C mutant lung cancer patients were treated with 180 mg (n=3) or 360 mg (n=1) doses. Objective responses were see… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 5 | submitted | EID9958In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to inhibit p-ERK a… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| Adagrasib + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11521Combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) shows remarkably enhanced anti… (full text at CIViC) PMID 37703579 · Khan et al., 2023 · Open in CIViC | civic |
| Afatinib + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9960In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| AMG511 + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9964In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| Carboplatin + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9965In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| Erlotinib + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID9961In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| RMC-4550 + SotorasibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9962In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| Sotorasib + TrametinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9963In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumors and improved the anti-tumor efficacy of chemotherapy and targeted agents. AMG 510 was shown to cause synergist… (full text at CIViC) PMID 31666701 · Canon et al., 2019 · Open in CIViC | civic |
| Selumetinib + TizaterkibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9146In preclinical experiments using the KRAS G12C mutant NSCLC cell line NCI-H358, combination AZD0364 and selumetinib treatment showed synergistic effect as defined by a Loewe score >=5, as well as stro… (full text at CIViC) PMID 33273059 · Flemington et al., 2021 · Open in CIViC | civic |
| KRAS G12D5 | ||||||||
| Dabrafenib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 2 | accepted | EID91A 63 year old patient was diagnosed with lung adenocarcinoma and received several treatment regimens over approximately three years, including carboplatin/paclitaxel, erlotinib, pemetrexed/bevacizumab… (full text at CIViC) PMID 23524406 · Rudin et al., 2013 · Open in CIViC | civic |
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3955In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC | civic |
| KRAS G12D Inhibitor HRS-4642 | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| KRAS G12D + MET Splice Site (c.2888_3028del)METKRAS1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 2 | submitted | EID11461A 45-year old male (heavy smoker) presented with stage IV NSCLC (moderately differentiated adenocarcinoma. Sanger sequencing revealed a MET exon 14 splice site mutation (c.2888_3028del) and KRAS G12D … (full text at CIViC) PMID 27257131 · Liu et al., 2016 · Open in CIViC | civic |
| KRAS G12D + TSC1 Loss-of-functionKRASTSC11 | ||||||||
| Sirolimus | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID154Following rapamycin treatment of mice with KrasG12D-induced lung adenocarcinomas, mice with Tsc1 deletion (exon17/18 deletion resulting in frameshift) in the lung exhibit increased overall survival, i… (full text at CIViC) PMID 19966866 · Liang et al., 2010 · Open in CIViC | civic |
| KRAS G12/G131 | ||||||||
| Erlotinib + GefitinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID35In 60 patients with NSCLC, Exon 2 KRAS mutations were associated with resistance to the EGFR kinase inhibitors gefitinib or erlotinib (9/38 refractory vs 0/21 sensitive patients; P=0.0201). PMID 15696205 · Pao et al., 2005 · Open in CIViC | civic |
| KRAS G12R2 | ||||||||
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3993In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3995In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC | civic |
| KRAS G12S7 | ||||||||
| Dasatinib | Lung Squamous Cell Carcinoma | Predictive | D | Supports Resistance | — | submitted | EID4020In an in vitro study, the A549 cell line, which harbors the KRAS G12S mutation, was found to have insensitivity to dasatinib treatment (IC50: 7.4 uM). In in vivo experiments, KRAS G12S expressing A549… (full text at CIViC) PMID 22328973 · Hammerman et al., 2011 · Open in CIViC | civic |
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID4013In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| KRAS G12V6 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID987Retrospective analysis of data from 841 patients who underwent surgery and molecular testing for NSCLC. Mutant KRAS was observed in 265 (31.5%) cases and 90 of these were G12V. Patients with KRAS G12… (full text at CIViC) PMID 26372703 · Renaud et al., 2015 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 3 | submitted | EID8891This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One patient harbored KRAS G12V co-mutation … (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC | civic |
| Docetaxel + SelumetinibCombination | ||||||||
| KRAS G13C2 | ||||||||
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3901In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3902In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC | civic |
| KRAS G13D2 | ||||||||
| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3892In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3893In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC | civic |
| 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 Mutation8 | ||||||||
| (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 | |||||
Data updated 9 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 |
| B |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID12137Zhou, C., et al. developed a novel KRAS G12D inhibitor, HRS-4642, and found that in preclincial experiments, HRS-4642 effectively reduced tumor growth compared to controls. After preclinical success, … (full text at CIViC) PMID 38942026 · Zhou et al., 2024 · Open in CIViC |
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| Dactolisib + SelumetinibCombination | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID305The use of NVP-BEZ235 in conjunction with ARRY-142886, but not as monotherapy, in a lung cancer mouse model with an inducible KRAS G12D mutation (lox-stop-lox KRAS G12D floxed via inhaled adenoviral C… (full text at CIViC) PMID 19029981 · Engelman et al., 2008 · Open in CIViC | civic |
| Setidegrasib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12937A phase 1 dose‑escalation and dose‑expansion study in patients with previously treated advanced KRAS p.G12D mutant NSCLC (NCT05382559; n = 203 overall; n = 45 NSCLC treated at the recommended phase 2 … (full text at CIViC) PMID 41879829 · Park et al., 2026 · Open in CIViC | civic |
| C |
| Supports Resistance |
| — |
| submitted |
EID4017In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4018In an in vitro study, �an A549 non-small cell lung cancer cell line expressing KRAS G12S mutation (endogenous expression) demonstrated resistance to erlotinib treatment compared to SK-MES-1 and H661 c… (full text at CIViC) PMID 24351425 · Toulany et al., 2014 · Open in CIViC | civic |
| MUC1-targeted Peptide GO-203-2C | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID7178Non-small cell lung cancers (NSCLCs) that harbor an oncogenic KRAS mutation are often associated with resistance to targeted therapies. MUC1-C transmembrane protein is aberrantly over-expressed in NSC… (full text at CIViC) PMID 25245423 · Kharbanda et al., 2014 · Open in CIViC | civic |
| PI103 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7050In A549, a gefitinib-resistant NSCLC cell line that harbors KRAS G12S, PI103 reduced cell growth and blocked cell cycle progression. PMID 19513541 · Zou et al., 2009 · Open in CIViC | civic |
| Vemurafenib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID4019In an in vitro study, the A549 cell line expressing a KRAS G12S mutation was associated with resistance to vemurafenib treatment. Resistance was determined by assessing cell viability and phosphorylat… (full text at CIViC) PMID 25706985 · Joshi et al., 2015 · Open in CIViC | civic |
| Predictive |
| B |
| Supports Sensitivity Response |
| 1 |
| accepted |
EID114383 patients from a phase II trial (docetaxel + placebo or selumetinib) with KRAS mutant tumors were retrospectively assessed for differences in OS, PFS, ORR and change in tumor size at week 6 accordin… (full text at CIViC) PMID 26125448 · Jänne et al., 2015 · Open in CIViC |
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| Erlotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3927In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3928In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC | civic |
| Palbociclib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID795In vivo studies confirmed the activity of PD0332991 (CDK4 inhibitor) on KRAS G12V mutant tumors. 17% (2/12) of mice treated with PD0332991 developed detectable lesions, whereas 75% of mice (3/4) treat… (full text at CIViC) PMID 20609353 · Puyol et al., 2010 · Open in CIViC | civic |
| 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 |