Cancer Family
Malignant Digestive System Neoplasm
CI-CAN-00000229Explore in graph →
4,262 active trials43 approved drugs556 evidence items
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Cancer Family
CI-CAN-00000229Explore in graph →
Variants & evidence
1,218 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 A146T7 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID2943Preclinical data supporting resistance of Exon 4 mutations, in particular A146T, to cetuximab and sensitivity to PD0325901. This study involved treatment of mice bearing A146T KRAS xenografts treated … (full text at CIViC) PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID7176identified a KRAS(A146T) mutation after four passages in increasing concentrations of cetuximab (20 nM and higher; These cells were indeed resistant to the drug. These mutations that arise are the res… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC | civic |
| Cetuximab + FOLFOX-4 RegimenCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID3858In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations and wildtype BRAF (n=10), including A146T (N=3), G15D (N=1), and V152M/NRAS V160A, tr… (full text at CIViC) PMID 25666295 · Kaczirek et al., 2015 · Open in CIViC | civic |
| Cetuximab + IrinotecanCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 3 | submitted | EID3859In 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 + PD98059Substitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID12070Colorectal cancer cell line HT29 was invected with KRAS lentivirus constructs for wildtype, A146V, A146T, A146P, and empty. Cells were treated with the anti-EGFR monoclonal antibody cetuximab, and MEK… (full text at CIViC) PMID 30448735 · Seol et al., 2019 · Open in CIViC | civic |
| Dactolisib + SelumetinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2206In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC | civic |
| Mirdametinib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID2944Preclinical data supporting resistance of Exon 4 mutations, in particular A146T, to cetuximab and sensitivity to PD0325901. PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC | civic |
| KRAS A146V2 | ||||||||
| Cetuximab + PD98059Substitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID12069Colorectal cancer cell line HT29 was invected with KRAS lentivirus constructs for wildtype, A146V, A146T, A146P, and empty. Cells were treated with the anti-EGFR monoclonal antibody cetuximab, and MEK… (full text at CIViC) PMID 30448735 · Seol et al., 2019 · Open in CIViC | civic |
| Dactolisib + SelumetinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2209In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring NRAS, KRAS, BRAF or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC | civic |
| KRAS Activating Mutation3 | ||||||||
| Inhibitor | Malignant Pancreatic Neoplasm | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7182Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS-PDEδ interaction that inhibit oncogenic RAS signalling and suppress in vitro and in vivo prolifera… (full text at CIViC) PMID 23698361 · Zimmermann et al., 2013 · Open in CIViC | civic |
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination | Malignant Pancreatic Neoplasm | Predictive | D | Supports Sensitivity Response | 1 | submitted | EID7184MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Combinations of MEK and EGFR inhibitors induced apoptosis. Combinatorial effect was observed in the epithelial but not mesenchymal subt… (full text at CIViC) PMID 23918833 · Mirzoeva et al., 2013 · Open in CIViC | civic |
| KRAS Amplification2 | ||||||||
| Cetuximab + EncorafenibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID2928Paired pre-treatment and post-progression tumor biopsies from BRAF-mutant CRC patients treated with RAF inhibitor combinations were analyzed. Alterations in MAPK pathway genes were found in resistant … (full text at CIViC) PMID 25673644 · Ahronian et al., 2015 · Open in CIViC | civic |
| Cetuximab + Panitumumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7105Screening of 1,039 CRC samples to assess the prevalence of KRAS amplification and the role of this genetic alteration on the sensitivity to anti EGFR therapies. KRAS amplification was mutually exclusi… (full text at CIViC) PMID 23404247 · Valtorta et al., 2013 · Open in CIViC | civic |
| KRAS Exon 2 Mutation11 | ||||||||
| (prognostic) | Pancreatic Carcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID917KRAS exon 2 was mutated in 121 of 173 patients with advanced pancreatic cancer. Patients with KRAS wildtype had an improved OS (HR 1.68, p = 0.005). PMID 23435671 · Boeck et al., 2013 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID2361This retrospective study examines outcomes of 158 primary sporadic colorectal cancer patients who had undergone surgical resection and were treated with 5-fluorouracil based chemotherapy. KRAS exon 2 … (full text at CIViC) PMID 17590872 · Kato et al., 2007 · Open in CIViC | civic |
| 〃 | Rectal CarcinomaALIAS | Prognostic | B | Does Not Support | ||||
| KRAS Exon 2 Mutation + Low1 | ||||||||
| (prognostic) | Colon Carcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID120735577 colon carcinoma tumors were evaluated for BRAF, KRAS, and mismatch repair status. From those successfully evaluated, 201 had microsatellite instability (MSI or MSI-H) and BRAF V600E, 72 had MSI a… (full text at CIViC) PMID 28040692 · Taieb et al., 2017 · Open in CIViC | civic |
| KRAS EXON 2 Mutations1 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | submitted | EID110531,404 Formalin-fixed paraffin-embedded tissue blocks were prospectively screened from patients over 18 with stage II or III adenocarcinoma of the colon completely resected. Patient samples were scre… (full text at CIViC) PMID 20008640 · Roth et al., 2010 · Open in CIViC | civic |
| KRAS G10_A11insG1 | ||||||||
| (oncogenic) | Malignant Colorectal NeoplasmCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 4 | accepted | EID9330FFPE tumor tissue from 1506 colorectal cancer patients was analyzed at codons 12, 13, 61 and 146 by PCR. 672 KRAS mutations were found in 670 patients, and from these, two were inframe insertions loca… (full text at CIViC) PMID 24642870 · Tong et al., 2014 · Open in CIViC | civic |
| KRAS G122 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Does Not Support Better Outcome | 4 | accepted | EID336In patients with stage III colorectal cancer undergoing chemotherapy, KRAS G12 mutation did not impact overall or disease free survival. PMID 19934290 · Ogino et al., 2009 · Open in CIViC | civic |
| Mitogen-Activated Protein Kinase Kinase Inhibitor | Malignant Pancreatic Neoplasm | Predictive | D | Supports Resistance | 2 | submitted | EID7183Preclinical study shows strong correlation between KRAS mutational subtype and CNV, and sensitivity to MEK inhibition. Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times … (full text at CIViC) PMID 25167228 · Hamidi et al., 2014 · Open in CIViC | civic |
| KRAS G12A19 | ||||||||
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID4429This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 22 patients harbored KRAS G12A, were BRAF, NRAS and PIK3CA wt, and had individual response… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3699In a retrospective study of 30 metastatic colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=13) treated with cetuximab and standard chemotherapy were associated with an absen… (full text at CIViC) PMID 16618717 · Lièvre et al., 2006 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | |||||||
| KRAS G12C1 | ||||||||
| Adagrasib + CetuximabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID12063The efficacy of adagrasib + cetuximab combination therapy was tested in 94 patients harbouring colorectal cancers with KRAS G12C mutations. ORR was used as the primary end-point for the study. The ORR… (full text at CIViC) PMID 38587856 · Yaeger et al., 2024 · Open in CIViC | civic |
Data updated 15 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.
| Malignant Pancreatic Neoplasm |
| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID7180Evaluation of the effectiveness of salirasib in preclinical models and patients with metastatic pancreatic adenocarcinoma (PDA). Preclinical study treated with salirasib alone and in combination with … (full text at CIViC) PMID 22547163 · Laheru et al., 2012 · Open in CIViC |
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| 2 |
| accepted |
EID4052This study examined outcomes of 240 rectum cancer patients treated with total mesorectal excision therapy. Tumor samples were obtained at the time of surgery and genotyped for KRAS exon 2 mutations (l… (full text at CIViC) PMID 19903786 · He et al., 2009 · Open in CIViC |
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| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 5 | accepted | EID993KRAS mutation status was assessed in 394 tumor samples from colorectal cancer patients who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone. 42% of… (full text at CIViC) PMID 18946061 · Karapetis et al., 2008 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID250Patients with colorectal cancer who harbor KRAS mutation have low response rate to cetuximab. PMID 16618717 · Lièvre et al., 2006 · Open in CIViC | civic |
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID1208102 mCRC patients treated with anti-EGFR therapy were analyzed for 34 hotspot mutations in KRAS, NRAS and BRAF with nanofluidic digital PCR and quantitative PCR. dPCR and qPCR results were correlated … (full text at CIViC) PMID 27037411 · Azuara et al., 2016 · Open in CIViC | civic |
| Erlotinib | Pancreatic Carcinoma | Predictive | B | Does Not Support Resistance | 3 | accepted | EID916KRAS exon 2 was mutated in 121 of 173 (70%) patients with advanced pancreatic cancer and did not show an association with response to erlotinib treatment. PMID 23435671 · Boeck et al., 2013 · Open in CIViC | civic |
| Erlotinib + GemcitabineCombination | Malignant Pancreatic Neoplasm | Predictive | B | Supports Resistance | 4 | accepted | EID1219In a retrospective study of 136 pancreatic cancer patients, point mutations in KRAS exon 2 were associated with worse overall survival compared to that of wild-type KRAS (5.8 vs 8.0 months; P = 0.001;… (full text at CIViC) PMID 21862683 · Kim et al., 2011 · Open in CIViC | civic |
| Irinotecan + SelumetinibCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 1 | accepted | EID132631 patients with KRAS exon 2 mutation (codons 12 and 13) were treated with selumetinib and irinotecan. All patients had ECOG status 0 or 1 and confirmed progression after first line therapy with oxali… (full text at CIViC) PMID 25322874 · Hochster et al., 2015 · Open in CIViC | civic |
| Regorafenib Anhydrous | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 1 | accepted | EID87KRAS mutation status was not predictive of response to regorafenib treatment in patients that had received standard therapy and progressed within 3 months of their last treatment. KRAS exon 2 variants… (full text at CIViC) PMID 24559322 · Sartore-Bianchi et al., 2014 · Open in CIViC | civic |
| Vemurafenib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID8367This preclinical study examined vemurafenib efficacy on various colorectal cancer cell lines and in vivo via mouse xenograft experiments. Three cell lines harbored KRAS exon 2 mutations and wt BRAF: H… (full text at CIViC) PMID 22180495 · Yang et al., 2012 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Resistance |
| — |
| submitted |
EID3700In a retrospective study of 113 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation treated with cetuximab plus irinotecan (34/83) were associated… (full text at CIViC) PMID 17998284 · De Roock et al., 2008 · Open in CIViC |
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| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | rejected | EID3701In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with second-line or higher cetuximab therapy in combination with standard ch… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3702In 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 | EID3703In 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 Resistance | — | submitted | EID3705In a retrospective study of 572 advanced colorectal cancer patients, patients treated with cetuximab and best supportive care with a KRAS exon 2 mutation (81/164) were associated with reduced response… (full text at CIViC) PMID 18946061 · Karapetis et al., 2008 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3706In a phase 3 clinical study of 1,198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI were associated with reduced overal… (full text at CIViC) PMID 21502544 · Van Cutsem et al., 2011 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3707In a phase 2 clinical study of 344 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFOX-4 (n=52) were associated with reduced … (full text at CIViC) PMID 19114683 · Bokemeyer et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3708In a retrospective study of 95 metastatic colorectal cancer patients, patients harboring KRAS activating mutation (n=33) and treated with cetuximab plus standard chemotherapy were reportedly non-respo… (full text at CIViC) PMID 20010090 · Yen et al., 2010 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | submitted | EID3709In a phase 3 clinical study (NCT00154102) of 1198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI (n=105) were associate… (full text at CIViC) PMID 19339720 · Van Cutsem et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Colon Neoplasm | Predictive | C | Supports Resistance | — | submitted | EID3717In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12A mutation (n=49) and treated with cetuximab plus standard chemotherapy were associated with decreased dis… (full text at CIViC) PMID 24687927 · Yoon et al., 2014 · Open in CIViC | civic |
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 2 | accepted | EID6319In 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 … (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC | civic |
| Panitumumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | rejected | EID2005KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | rejected | EID2006KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | — | rejected | EID2007KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC | civic |
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Resistance | 2 | submitted | EID6325KRAS G12A was the only variant noted in the primary tumor of one metastatic colorectal cancer patient who experienced stable disease following treatment with anti-epidermal growth factor receptor (EGF… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC | civic |
| Regorafenib Anhydrous | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 2 | accepted | EID3710In an in vitro study, a human colon adenocarcinoma SW48 cell line virally transduced to express KRAS G12A demonstrated resistance to regorafenib treatment (IC50: 330.13 nM vs. 114.28 nM, P<0.01, repor… (full text at CIViC) PMID 26161928 · Camaj et al., 2015 · Open in CIViC | civic |
| Sunitinib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | — | submitted | EID3711In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12A mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 6.5uM vs. 2.6uM, P<0.05) compared to SW48 cells expr… (full text at CIViC) PMID 23455880 · Modest et al., 2013 · Open in CIViC | civic |