Cancer Family
Respiratory System Neoplasm
CI-CAN-00000049Explore in graph →
Non-malignant2,725 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 |
|---|---|---|---|---|---|---|---|---|
| ROS1 Fusion1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1690In an evaluation of a patient and never smoker with crizotinib-sensitive lung adenocarcinoma, an SDC4-ROS1 rearrangement was identified using comprehensive genomic profiling. The patient attained a de… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC | civic |
| EGFR Fusion1 | ||||||||
| Cetuximab + GefitinibCombination | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID10899Case report describing a patient with NSCLC and EGFR(ex25)::Intergenic Region of SEC61G(breakpoint 32 aa downstream of SEC61G) fusion and concurrent EGFR amplification with treatment response to a com… (full text at CIViC) PMID 34342091 · Zhang et al., 2021 · Open in CIViC | civic |
| NRG1 Fusion1 | ||||||||
| Afatinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7491A 42 year old nonsmoker with metastatic lung adenocarcinoma that was wild-type for EGFR, KRAS, ROS1, and ALK, was found to have re-arranged NRG1. Treatment with afatanib resulted in rapid symptomatic … (full text at CIViC) PMID 28502724 · Gay et al., 2017 · Open in CIViC | civic |
| SLFN11 EXPRESSION1 | ||||||||
| Talazoparib + TemozolomideCombination | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5883SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC as well as combinatorial therapy with TMZ. PMID 27440269 · Lok et al., 2017 · Open in CIViC | civic |
| SMAD4 Underexpression1 | ||||||||
| Gemcitabine | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID6437Of the 28 individuals that received 30 treatments containing gemcitabine or etoposide, only 13 of them showed underexpression of SMAD4. Treatment with DNA topoisomerase inhibitors, especially gemcitab… (full text at CIViC) PMID 28577946 · Ziemke et al., 2017 · Open in CIViC | civic |
| SMARCA4 INACTIVATING MUTATION2 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID513In patients with lung adenocarcinoma, those with loss-of-function mutations in SMARCA4 had worse overall survival than those with only missense or no mutations. PMID 24658004 · Jelinic et al., 2014 · Open in CIViC | civic |
| Tozasertib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5928AURKA activity is essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mous… (full text at CIViC) PMID 28102363 · Tagal et al., 2017 · Open in CIViC | civic |
| SMARCA4 Loss1 | ||||||||
| Abemaciclib + PalbociclibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID7155Preclinical evidence showing that SMARCA4 inactivation results in downregulation of Cyclin D1 in NSCLC cells and confers sensitivity of such to CDK4/6 inhibitors. SMARCA4 loss is synthetic letha with … (full text at CIViC) PMID 30718506 · Xue et al., 2019 · Open in CIViC | civic |
| SMARCA4 Underexpression2 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID838SMARCA4 expression was determined with gene expression microarray in 133 patients. Reduced overall survival was observed in patients with low SMARCA4 expression compared to intermediate (P<0 .001) or … (full text at CIViC) PMID 26671993 · Bell et al., 2016 · Open in CIViC | civic |
| Cisplatin + VinorelbineCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID837SMARCA4 expression was determined with gene expression microarray in 133 patients. Improved five-year disease-specific survival (DSS) was noted only in patients with low SMARCA4 expression when treate… (full text at CIViC) PMID 26671993 · Bell et al., 2016 · Open in CIViC | civic |
| SMO Amplification2 | ||||||||
| Gefitinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID2945Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibit… (full text at CIViC) PMID 26124204 · Della Corte et al., 2015 · Open in CIViC | civic |
| Gefitinib + SonidegibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID2946Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibit… (full text at CIViC) PMID 26124204 · Della Corte et al., 2015 · Open in CIViC | civic |
| NTRK1 Fusion3 | ||||||||
| Entrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1868In 1378 cases of NSCLC screened for NTRK1 rearrangements, 2 were identified (frequency 0.1%). One patient with SQSTM1-NTRK1 was treated with entrectinib in a phase 1 study. The patient had resolution … (full text at CIViC) PMID 26565381 · Farago et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID2950Two 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 anti… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| Larotrectinib | Lung Adenocarcinoma | |||||||
| STK11 EXON 1-2 MUTATION1 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID750In a retrospective analysis of 567 non-squamous, non-small cell lung cancer patients, Exon 1-2 mutations in STK11 were significantly associated with shorter OS (24 vs. 69 months) also after multivaria… (full text at CIViC) PMID 26625312 · Pécuchet et al., 2017 · Open in CIViC | civic |
| STK11 Loss2 | ||||||||
| Docetaxel + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1144A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-beari… (full text at CIViC) PMID 22425996 · Chen et al., 2012 · Open in CIViC | civic |
| Everolimus + SirolimusSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID1620Preclinical study in 5 NSCLC cell lines. Two LKB1 (STK11) mutant cell lines had higher basal levels of mTOR activity (pS6K and p4EBP1 levels) but were not more sensitive to mTOR inhibitors (everolimus… (full text at CIViC) PMID 26027660 · Xiao et al., 2015 · Open in CIViC | civic |
| STK11 Loss10 | ||||||||
| MEK Inhibitor CI-1040 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2319STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 15021901 · Carretero et al., 2004 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2320STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 21102257 · Marcus et al., 2010 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | |||||
| STK11 Mutation5 | ||||||||
| Chemoradiotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12911In a retrospective cohort of stage III NSCLC treated with definitive radiotherapy with or without concurrent chemotherapy (n = 164), somatic STK11 (LKB1) mutations (n = 12) were associated with higher… (full text at CIViC) PMID 33323404 · Sitthideatphaiboon et al., 2021 · Open in CIViC | civic |
| Cisplatin/Pembrolizumab/Pemetrexed Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | submitted | EID12338A retrospective analysis of 871 non-squamous NSCLC patients treated with chemotherapy (platinum compound plus pemetrexed) combined with immunotherapy (pembrolizumab) found that those with STK11 mutati… (full text at CIViC) PMID 39385035 · Skoulidis et al., 2024 · Open in CIViC | civic |
| Atezolizumab | ||||||||
| KEAP1 Mutation + STK11 MutationSTK11KEAP11 | ||||||||
| Cisplatin/Pembrolizumab/Pemetrexed Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12340A retrospective analysis of 871 non-squamous NSCLC patients treated with chemotherapy (platinum compound plus pemetrexed) combined with immunotherapy (pembrolizumab) found that those with STK11 or KEA… (full text at CIViC) PMID 39385035 · Skoulidis et al., 2024 · Open in CIViC | civic |
| KEAP1 G417W + STK11 Rearrangement exon 1STK11KEAP11 | ||||||||
| Chemoimmunotherapy + Palliative Radiation TherapySequential | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | submitted | EID12933In a case report of KRAS wild‑type NSCLC (n = 1, age 53 male) a tumor harbored concurrent STK11 (rearrangement exon 1) and KEAP1 (G417W) mutations, along with additional somatic alterations (including… (full text at CIViC) PMID 36858519 · Sumii et al., 2023 · Open in CIViC | civic |
| H-bTMB1 | ||||||||
| Immune Checkpoint Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12724The use of circulating tumor DNA in blood for TMB assessment was tested. The cancer gene panel NCC-GP150, which covers the whole exon regions of 150 genes, was created and tested for correlation again… (full text at CIViC) PMID 30816954 · Wang et al., 2019 · Open in CIViC | civic |
| High14 | ||||||||
| Atezolizumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12587This retrospective study evaluated the clinical utility of blood tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab efficacy in advanced non-small cell lung cancer (NSCLC) who … (full text at CIViC) PMID 30082870 · Gandara et al., 2018 · Open in CIViC | civic |
| Chemotherapy + ToripalimabCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12798This is part of a multi-centred, randomised, placebo-controlled phase 3 trial, CHOICE-01, that examined therapeutic response to first-line chemotherapy plus PD-1 inhibitor in non-small cell lung cance… (full text at CIViC) PMID 39255777 · Xu et al., 2024 · Open in CIViC | civic |
| Durvalumab | ||||||||
Data updated 20 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.
| C |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID11574Drilon et al (2022) assessed the efficacy and safety of larotrectinib in lung cancer patients with TRK fusions in a phase II adult/young adult trial (NCT02576431) and a phase I adult trial (NCT0212291… (full text at CIViC) PMID 35085007 · Drilon et al., 2022 · Open in CIViC |
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| Supports Sensitivity Response |
| — |
| rejected |
EID2321STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 12097271 · Sanchez-Cespedes et al., 2002 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2322STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 18948947 · Ding et al., 2008 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID2318NSCLC cell lines that contain inactivating STK11 mutations and activating KRAS mutations have shown a reduced proliferation rate in response to the MEK inhibitor CI-1040 (P<0.001) compared to NSCLC ce… (full text at CIViC) PMID 19165201 · Mahoney et al., 2009 · Open in CIViC | civic |
| Sirolimus | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2314STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 15021901 · Carretero et al., 2004 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2315STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 21102257 · Marcus et al., 2010 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2316STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 12097271 · Sanchez-Cespedes et al., 2002 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2317STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 18948947 · Ding et al., 2008 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID2313NSCLC cell lines that contain inactivating STK11 mutations and activating KRAS mutations have shown a reduced proliferation rate in response to the MEK inhibitor CI-1040 (P<0.001) compared to NSCLC ce… (full text at CIViC) PMID 19165201 · Mahoney et al., 2009 · Open in CIViC | civic |
| Lung Adenocarcinoma |
| Predictive |
| B |
| Supports Resistance |
| 4 |
| accepted |
EID6441In a retrospective analysis in two separate datasets (Stand Up To Cancer 2 Cohort and Checkmate-057), patients with concomitant KRAS and STK11 mutations had significantly worse response rates, PFS and… (full text at CIViC) PMID 29773717 · Skoulidis et al., 2018 · Open in CIViC |
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| Radiation Therapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | submitted | EID12912In retrospective analyses of multiple non‑metastatic NSCLC cohorts (TCGA PanCancer n = 736, MSK‑IMPACT n = 961, TRACERx n = 100), pathogenic STK11 mutations were associated with worse outcomes only in… (full text at CIViC) PMID 35958336 · Kinslow et al., 2022 · Open in CIViC | civic |
| Vistusertib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 2 | accepted | EID12514In a phase II trial of 49 NSCLC patients with STK11 mutation, the MTORC1/2 inhibitor vistusertib did not result in any responses. PMID 40069402 · Middleton et al., 2025 · Open in CIViC | civic |
| Lung Non-Small Cell CarcinomaCURATED_BROADER |
| Predictive |
| B |
| Does Not Support Sensitivity Response |
| 3 |
| accepted |
EID12799This is part of a open-label phase 3 trial, NEPTUNE, that examined therapeutic response to first-line durvalumab plus tremelimumab in patients with metastatic non-small cel lung cancer (NSCLC). 823 pa… (full text at CIViC) PMID 36240972 · de Castro et al., 2023 · Open in CIViC |
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| Durvalumab/Tremelimumab Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID12822The MYSTIC study compared response rates for immunotherapy verses chemotherapy. Specifically looking at the efficacy of the anti-PD-L1 therapy, durvalumab, with/without the anti-CTLA-4 therapy, tremel… (full text at CIViC) PMID 33355200 · Si et al., 2021 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID12760This exploratory analysis of the Phase 3 MYSTIC trial (NCT02453282) evaluated blood tumour mutational burden (bTMB) as a predictive biomarker for first-line durvalumab with or without tremelimumab vs … (full text at CIViC) PMID 32271377 · Rizvi et al., 2020 · Open in CIViC | civic |
| Immune Checkpoint Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13061This retrospective study evaluated the predictive value of tumor mutational burden (TMB) for immune checkpoint inhibitor (ICI) outcomes in 97 patients with stage IV non-small cell lung cancer who had … (full text at CIViC) PMID 38950679 · Di Federico et al., 2024 · Open in CIViC | civic |
| Immunotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13032A retrospective cohort study was performed with advanced NSCLC patients who had prior immunotherapy with available genomic testing, and TMB determined by NGS via the Foundation Medicine assay. 87 pati… (full text at CIViC) PMID 33972172 · Kao et al., 2021 · Open in CIViC | civic |
| Ipilimumab/Nivolumab Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | rejected | EID12612This part of the open-label multipart phase 3 trial, CheckMate 277 (Trial ID: 29658845), examined the performance of nivolumab plus ipilimumab compared to chemotherapy among non-small-cell lung cancer… (full text at CIViC) PMID 29658845 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12614This part of the open-label multipart phase 3 trial, CheckMate 277 (Trial ID: 29658845), examined the performance of nivolumab plus ipilimumab compared to chemotherapy among non-small-cell lung cancer… (full text at CIViC) PMID 29658845 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID13103Whole-exome sequencing-derived tumor mutational burden (TMB) was obtained from 75 patients recruited as part of the the CheckMate-012 trial (phase 1, open label, multicenter clincal trial of nivolumab… (full text at CIViC) PMID 29657128 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID12588This retrospective analysis assessed the association between tumor mutational burden (TMB) and the efficacy of nivolumab plus low-dose ipilimumab as first-line treatment for advanced/metastatic non-sm… (full text at CIViC) PMID 30785829 · Ready et al., 2019 · Open in CIViC | civic |
| Nivolumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12967In an exploratory analysis of the phase III CheckMate 026 trial in previously untreated stage IV or recurrent non-small-cell lung cancer, patients with high tumor mutational burden (≥243 missense muta… (full text at CIViC) PMID 28636851 · Carbone et al., 2017 · Open in CIViC | civic |
| PD1 Inhibitor + PD-L1 InhibitorSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12586High Tumor Mutation Burden (TMB >19 mutations/Mb) represents a robust and platform-validated genomic biomarker predictive of clinical benefit from PD-1/PD-L1 immune checkpoint blockade in non–small ce… (full text at CIViC) PMID 35708671 · Ricciuti et al., 2022 · Open in CIViC | civic |
| Pembrolizumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12083Exomes were sequenced from two cohorts of non small cell lung cancer patients who were treated with pembrolizumab. In a discovery cohort of 16 patients, durable clinical benefit (DCB - partial or stab… (full text at CIViC) PMID 25765070 · Rizvi et al., 2015 · Open in CIViC | civic |