Subtype
Malignant Intestinal Neoplasm
CI-CAN-00001137Explore in graph →
1,666 active trials21 approved drugs383 evidence items
- NCIt
- C4572
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Subtype
CI-CAN-00001137Explore in graph →
Variants & evidence
823 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 G13R2 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3906In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC) PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3907In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC) PMID 18202412 · Lièvre et al., 2008 · Open in CIViC | civic |
| KRAS G13S3 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | rejected | EID3908In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with cetuximab as salvage therapy (second-line therapy or higher) in combina… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3909In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC) PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | |||||||
| KRAS G13V3 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | — | submitted | EID4508In a retrospective study of 23 EGFR-expressing metastatic colorectal cancer patients, patients with KRAS codon G12 or G13 mutations (n=6) treated with cetuximab were associated with decreased partial … (full text at CIViC) PMID 17363584 · Benvenuti et al., 2007 · Open in CIViC | civic |
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 2 | accepted | EID6312In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS PIK3CA and PTEN we… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC | civic |
| Cetuximab | ||||||||
| KRAS KRAS4A underexpression2 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9598In a clinical study including 285 patients, KRAS4A low expression is significantly correlated with reduced OS by a multivariate analysis (p = 0.0038). Such significant correlation is observed in the w… (full text at CIViC) PMID 19824059 · Abubaker et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9599In a clinical study including 151 patients expressing KRAS WT, KRAS4A low expression is significantly correlated with reduced OS by a multivariate analysis (p = 0.018). Such significant correlation is… (full text at CIViC) PMID 30121958 · Eilertsen et al., 2019 · Open in CIViC | civic |
| KRAS Mutation16 | ||||||||
| Bevacizumab + ChemotherapyCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID1139Meta-Analysis of 12 studies with 2,266 patients (54 % were KRAS wt). The pooled response rates (RR) for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P… (full text at CIViC) PMID 23828442 · Petrelli et al., 2013 · Open in CIViC | civic |
| Binimetinib + PalbociclibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID4869A preclinical study to investigate the efficacy of Binimetinib, Palbociclib and the combination on KRAS mutant colorectal cancer cell lines, cell line-derived and patient-derived xenografts. The com… (full text at CIViC) PMID 27167191 · Lee et al., 2016 · Open in CIViC | |
| KRAS Q22*1 | ||||||||
| Panitumumab | Colon Mucinous Adenocarcinoma | Predictive | C | Supports Resistance | 2 | accepted | EID1131A 43-year-old female was diagnosed with an adenocarcinoma of the ascending colon and received 6-months of adjuvant chemotherapy. After 5 years of completion of adjuvant chemotherapy, the disease relap… (full text at CIViC) PMID 19661358 · Palmirotta et al., 2009 · Open in CIViC | civic |
| KRAS Q611 | ||||||||
| Cetuximab + ChemotherapyCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID3917This was a retrospective study of 605 patients with metastatic, chemotherapy refractory colorectal cancer treated with cetuximab + chemotherapy. Patients harboring KRAS codon 61 mutations (n=13) had a… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC | civic |
| KRAS Q61E3 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2807In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID4422In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| Irinotecan | Malignant Colorectal NeoplasmCURATED_BROADER | |||||||
| KRAS Q61FS3 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | submitted | EID2810In colorectal cancer patients, non-G12/G13 KRAS and NRAS mutations were associated with improved disease-free survival (n=186, P=0.006) compared to G12 and G13 KRAS mutations. None of the 12 Stage I-… (full text at CIViC) PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC | civic |
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2809In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | |||||||
| KRAS Q61H6 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2227In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3860In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal Neoplasm | |||||||
| KRAS Q61K3 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2230In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3871In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| Cetuximab + ChemotherapyCombination | ||||||||
| KRAS Q61L4 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2228In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3866In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal Neoplasm | |||||||
| KRAS Q61P3 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2805In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID4421In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC | civic |
| Cetuximab + IrinotecanSubstitutes | ||||||||
Data updated 11 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 |
| C |
| Supports Resistance |
| — |
| submitted |
EID3910In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC) PMID 18202412 · Lièvre et al., 2008 · Open in CIViC |
| civic |
| Malignant Colorectal NeoplasmCURATED_BROADER |
| Predictive |
| C |
| Supports Sensitivity Response |
| 1 |
| submitted |
EID6321KRAS G13V was the only variant noted in the metastatic tumor of one metastatic colorectal cancer patient who experienced partial response following treatment with anti-epidermal growth factor receptor… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC |
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| B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID988SiRNA 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 |
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID6464This study shows that KRAS mutations such as G12D, G13D and KRAS amplification are frequent drivers of acquired resistance to cetuximab in colorectal cancers. KRAS mutant clones can be detected throug… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1702A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC | civic |
| Cetuximab + ChemotherapyCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID3704This was a retrospective study of 605 patients with metastatic, chemotherapy refractory colorectal cancer treated with cetuximab + chemotherapy. Patients with KRAS mutant tumors (total [n = 253], codo… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC | civic |
| Cetuximab + DasatinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID947Combined treatment with dasatinib and cetuximab, but not either agent in monotherapy, had an antitumor efficacy in-vitro and in xenografts. These results were based on three KRAS mutant cell lines (LS… (full text at CIViC) PMID 20956938 · Dunn et al., 2011 · Open in CIViC | civic |
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 5 | accepted | EID5345NCCN guidelines indicate colorectal cancer patients with KRAS mutations should not be treated with the anti-EGFR therapies cetuximab or panitumumab. PMID 28275037 · Benson et al., 2017 · Open in CIViC | civic |
| Cetuximab + SelumetinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID4866A phase I study to determine the tolerability and pharmacokinetics of Selumetinib and Cetuximab with an expanded cohort in KRAS-mutant CRC. In the KRAS-mutant CRC dose expansion cohort 14 patients we… (full text at CIViC) PMID 26666244 · Deming et al., 2016 · Open in CIViC | civic |
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Immunomodulatory OligonucleotideCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID943TLR9 agonist immunomodulatory oligonucleotide (IMO) led to inhibited survival of LS174T colorectal cancer and AsPC1 pancreatic cancer cell lines with KRAS mutations. PMID 21890455 · Rosa et al., 2011 · Open in CIViC | civic |
| Ixazomib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 1 | accepted | EID1182Preclinical study in colorectal cancer xenografts. KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cell line. KRAS wild-type, but not KRAS mutant tumors were sensitive to proteasome… (full text at CIViC) PMID 26709701 · Chattopadhyay et al., 2015 · Open in CIViC | civic |
| MEK Inhibitor RO4987655 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 2 | accepted | EID998Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655). All 25 patients with KRAS mutant colorectal cancer experienced PD. Median days on treatment was 57 (5-269).… (full text at CIViC) PMID 24947927 · Zimmer et al., 2014 · Open in CIViC | civic |
| Metformin | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID8301A retrospective study of 2335 metastatic colorectal cancer (mCRC) patients, including 282 patients with type 2 diabetes mellitus (T2DM), examined the survival effects of metformin use in mCRC. Diabeti… (full text at CIViC) PMID 32444490 · Xie et al., 2020 · Open in CIViC | civic |
| Refametinib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Does Not Support Sensitivity Response | 2 | accepted | EID1001Phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766. 4 patients with KRAS +/- PIK3CA mutant colorectal cancer. 3 with SD, 1 with PD. PMID 23434733 · Weekes et al., 2013 · Open in CIViC | civic |
| Selumetinib + TeprotumumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1004Preclinial data from KRAS mutant colorectal cancer cell lines show syngergistic effect on cell viability and apoptosis in vitro and in vivo when MEK and IGF-IR are inhibited concomitantly. In other ce… (full text at CIViC) PMID 21985784 · Ebi et al., 2011 · Open in CIViC | civic |
| Afatinib + TrametinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID991An shDNA Screen identified synergy betwenn 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 |
| Predictive |
| B |
| Supports Resistance |
| — |
| submitted |
EID2808In colorectal cancer patients, non-G12/G13 KRAS and NRAS mutations were associated with improved disease-free survival (n=186, P=0.006) compared to G12 and G13 KRAS mutations. None of the 12 Stage I-… (full text at CIViC) PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC |
| civic |
| Predictive |
| C |
| Supports Resistance |
| — |
| submitted |
EID4423In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC |
| civic |
| Predictive |
| C |
| Supports Resistance |
| — |
| accepted |
EID3862In a colorectal cancer patient with a KRAS Q61H mutation, KRAS Q61H was reported to be refractory to cetuximab treatment. The patient was treated with cetuximab and irinotecan for 18 months, had a par… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC |
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| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3863In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring KRAS Q61L (n=2), Q61H (n=1), or A146T (n=2) mutations were reported to be non-responder… (full text at CIViC) PMID 26989027 · Hsu et al., 2016 · Open in CIViC | civic |
| Cetuximab + ChemotherapyCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 3 | accepted | EID3861Seven patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored KRAS Q61H (either c.183A > C or >T) and were wi… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC | civic |
| Panitumumab + TrametinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 3 | submitted | EID2970In a molecular case report, a KRAS Q61H mutation was found causing resistance to a combination therapy with panitumumab and the MEK inhibitor trametinib. PMID 26644315 · Russo et al., 2016 · Open in CIViC | civic |
| Malignant Colorectal NeoplasmCURATED_BROADER |
| Predictive |
| C |
| Supports Resistance |
| 3 |
| accepted |
EID3872Two patients participating in a large retrospective trial of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored KRAS Q61K. One patient was a 61 year old female w… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC |
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| Predictive |
| C |
| Supports Resistance |
| — |
| submitted |
EID3868In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring KRAS Q61L (n=2), Q61H (n=1), or A146T (n=2) mutations were reported to be non-responder… (full text at CIViC) PMID 26989027 · Hsu et al., 2016 · Open in CIViC |
| civic |
| Cetuximab + ChemotherapyCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 3 | accepted | EID3867Two patients participating in a large retrospective trial of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored KRAS Q61L. One patient, a 67 year old male, whose… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC | civic |
| Malignant Colorectal NeoplasmCURATED_BROADER |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| submitted |
EID7177Mutations in KRAS are associated with resistance to monoclonal antibodies that target EGFR in patients with colorectal cancer. [KRAS codon 61 mutations occur in approximately 1 – 4% of colorectal canc… (full text at CIViC) PMID 21575616 · French et al., 2011 · Open in CIViC |
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