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 |
|---|---|---|---|---|---|---|---|---|
| EGFR T415M1 | ||||||||
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7101Next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding… (full text at CIViC) PMID 29196463 · Strickler et al., 2018 · Open in CIViC | civic |
| EGFR T790M2 | ||||||||
| (prognostic) | Cholangiocarcinoma | Prognostic | B | Supports Better Outcome | 1 | submitted | EID10358In a Thai cohort of 81 patients with cholangiocarcinoma, 17 patients harbored EGFR variants, 9 of which were T790M. EGFR T790M variants were associated with longer overall survival than patients with … (full text at CIViC) PMID 29066915 · Trachu et al., 2017 · Open in CIViC | civic |
| Osimertinib | Pancreatic Adenocarcinoma | Predictive | C | Does Not Support Sensitivity Response | 2 | accepted | EID6006Patients with recurrent pancreatic adenocarcinoma was treated with gemcitabine + nab-paclitaxel, FOLFIRINOX and docetaxel + irinotecan. After failure of these treatment, a tumor specimen from the panc… (full text at CIViC) PMID 28874593 · Cecchini et al., 2017 · Open in CIViC | civic |
| EGFR V441D1 | ||||||||
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7095Next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding… (full text at CIViC) PMID 29196463 · Strickler et al., 2018 · Open in CIViC | civic |
| EGFR V441F1 | ||||||||
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | E | Supports Resistance | 2 | accepted | EID7096Next-generation sequencing data of cfDNA from 1,397 patients with colorectal cancer identified a novel cluster of extracellular domain (ECD). EGFR V441G/D/F mutations were found in 19% (n=8) of patien… (full text at CIViC) PMID 29196463 · Strickler et al., 2018 · Open in CIViC | civic |
| EGFR V441G1 | ||||||||
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7094Next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding… (full text at CIViC) PMID 29196463 · Strickler et al., 2018 · Open in CIViC | civic |
| EGFR Y69FS*111 | ||||||||
| Erlotinib | Esophageal Squamous Cell CarcinomaALIAS | Predictive | D | Supports Resistance | — | submitted | EID4808In an in vitro study, an esophageal squamous cell carcinoma cell line KYSE70 expressing EGFR Y69fs*11 mutation was associated with insensitivity to erlotinib treatment (IC50=4.31uM). Resistance was de… (full text at CIViC) PMID 27207775 · Nakamura et al., 2016 · Open in CIViC | civic |
| EIF4EBP1 PHOSPHORYLATION2 | ||||||||
| Everolimus | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID9188 gastric cancer cell lines were treated with the MTOR inhibitor everolimus. Cell proliferation was effectively inhibited in 3 cell lines by everolimus. Phosphorylated EIF4EBP1 (T37/46, T70) levels we… (full text at CIViC) PMID 23340172 · Nishi et al., 2013 · Open in CIViC | civic |
| Dactolisib + MTOR Kinase Inhibitor PP242 + WYE354Substitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 2 | accepted | EID93212 CRC cell lines were evaluated. 40% of these were intrinsically resistant to mTOR inhibition with BEZ235, PP242 or WYE354. mTOR independent phosphorylation of EIF4EBP1 (T37/46) was associated with … (full text at CIViC) PMID 22262166 · Zhang et al., 2012 · Open in CIViC | civic |
| ALK Fusion1 | ||||||||
| Nivolumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Does Not Support Resistance | 3 | submitted | EID7482One patient with colorectal cancer harboring MSI-High and EML4-ALK rearrangement received Nivolumab and achieved a durable response. PMID 29370427 · Pietrantonio et al., 2017 · Open in CIViC | civic |
| NTRK3 Fusion3 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID10484Whole genome sequencing and RNAseq were performed on 400 patients with resected or locally advanced/metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Immunohistochemistry (IHC) analysis was performe… (full text at CIViC) PMID 34583947 · Allen et al., 2023 · Open in CIViC | civic |
| 〃 | Colon Adenocarcinoma | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID10506From a retrospective review of 38,095 tumor samples from 33,997 patients using DNA sequencing (MSK-IMPACT) and RNA sequencing (MSK-Fusion panel) identified 87 tumors with NTRK1-3 fusions. Two cases of… (full text at CIViC) PMID 31375766 · Solomon et al., 2020 · Open in CIViC | civic |
| 〃 | Malignant Colon Neoplasm | Oncogenic | D | Supports Oncogenicity | 3 | |||
| EP300 Y1414C1 | ||||||||
| (oncogenic) | Esophageal Squamous Cell CarcinomaALIAS | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID9573Mutations in histone modifier genes were analyzed in exome sequence data from 113 esophageal squamous cell carcinoma tumors. KYSE-150 and KYSE-450 ESCC cell lines were depleted of EP300 using shRNA, t… (full text at CIViC) PMID 25151357 · Gao et al., 2014 · Open in CIViC | civic |
| EPAS1 Overexpression1 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID1033Expression of EPAS1 (HIF-2alpha) was assessed in 731 colorectal cancers from two prospective cohort studies. EPAS1 overexpression was found in 322 (46%) cancers by immunohistochemistry and not signifi… (full text at CIViC) PMID 20363910 · Baba et al., 2010 · Open in CIViC | civic |
| EPCAM c.556‐490_*8438del1 | ||||||||
| (predisposing) | Malignant Colorectal NeoplasmCURATED_BROADER | Predisposing | B | Supports Predisposition | 3 | submitted | EID115185 out of 224 Lynch syndrome unrelated patients (2%) presented an EPCAM deletion. All patients were diagnosed with colorectal cancer (CRC) at an early age (<50 years) and had a positive family history.… (full text at CIViC) PMID 30916491 · Cini et al., 2019 · Open in CIViC | civic |
| EPHB4 EXPRESSION1 | ||||||||
| Bevacizumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 2 | accepted | EID905EPHB4 expression, as assessed by quantitative RT-PCR in 13 colorectal cancer patients treated with bevacizumab, was higher in non-responders (p = 0.048). No difference was observed in a control group … (full text at CIViC) PMID 23579861 · Guijarro-Muñoz et al., 2013 · Open in CIViC | civic |
| ERBB2 Amplification29 | ||||||||
| (oncogenic) | Malignant Colorectal NeoplasmCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID11485Altered human epidermal growth factor receptor 2 (HER2) signaling caused by genomic amplification of ERBB2 or mutations is oncogenic and has been observed in multiple cancer types. Based on the study,… (full text at CIViC) PMID 29338072 · Ross et al., 2018 · Open in CIViC | civic |
| 〃 | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11563The ERRB2 amplification effect in PDAC was studied through CAPAN1 cells and ERBB2-KO (knockout) CAPAN1 cells that were KO using CRISPR (Figure 4C, Supp Table 4), with a 90% reduction of ERBB2 compared… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| Afatinib | Malignant Colorectal NeoplasmCURATED_BROADER | |||||||
| ERBB2 Amplification + ERBB2 Overexpression1 | ||||||||
| Chemotherapy + TrastuzumabCombination | Malignant Gastric Neoplasm | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID11255In this phase 3, open-label, randomized controlled trial, 594 patients (584 in the primary analysis) with HER2-positive amplification or overexpression gastric or gastroesophageal junction adenocarcin… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC | civic |
| ERBB2 E717D1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11555HPNE cells infected with lentiviral vectors containing the variant did show significant phosphorylation of ERBB2 (Supplementary Figure 1) compared to WT (Figure 2A and B). The variant also exhibits an… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| ERBB2 G292R1 | ||||||||
| (oncogenic) | Gallbladder Carcinoma | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID12117The ERBB2 G292R variant was observed in 1/57 normal/tumor pairs of human gallbladder carcinoma profiled by next-generation sequencing. Human gallbladder cancer cell lines (GBC-SD and NOZ) were transie… (full text at CIViC) PMID 24997986 · Li et al., 2014 · Open in CIViC | civic |
| ERBB2 L755S1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11557HPNE cells infected with lentiviral vectors containing the variant did show significant phosphorylation of ERBB2 (Supplementary Figure 1) compared to WT (Figure 2A and B). The variant also exhibits an… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
Data updated 1 hour 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.
| accepted |
EID10638From whole exome sequencing of 278 primary colon tumors with stage I-III, 2.5% carried gene fusion. 1.5% of these were positive for kinase fusions including BRAF, NTRK3 and RET gene fusions. These gen… (full text at CIViC) PMID 28512242 · Kloosterman et al., 2017 · Open in CIViC |
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| Predictive |
| D |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID7807Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was… (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC |
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| 〃 | Malignant Gastric Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID7808Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was … (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC | civic |
| 〃 | Pancreatic Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID962Afatinib was growth-inhibitory for three pancreatic cancer cell lines but cytotoxic only toward BxPC3 (KRAS wt) and Capan-2 (KRAS mut) cells, both of which express high levels of EGFR, ERBB2, and ERBB… (full text at CIViC) PMID 26668065 · Huguet et al., 2016 · Open in CIViC | civic |
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID1686A 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 |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID1687A 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 |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID1993We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF. All patients received cetuximab aft… (full text at CIViC) PMID 28223103 · Jeong et al., 2017 · Open in CIViC | civic |
| Capecitabine + Cetuximab + OxaliplatinCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Does Not Support Resistance | 1 | accepted | EID895141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 positive. These patients did not show a difference in outcome after capecitabine, oxaliplatin and ch… (full text at CIViC) PMID 24146218 · Sclafani et al., 2013 · Open in CIViC | civic |
| Cetuximab + PanitumumabSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 2 | accepted | EID1688HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitumumab. HER2 copy number status was significantly correlated with response rate, PFS and OS. Patients… (full text at CIViC) PMID 23348520 · Martin et al., 2013 · Open in CIViC | civic |
| Ibrutinib | Malignant Esophageal Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID6929This study found the clinical BTK/ERBB2 kinase inhibitor, ibrutinib, downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle a… (full text at CIViC) PMID 28830912 · Chong et al., 2018 · Open in CIViC | civic |
| Lapatinib | Gastric Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1023TyTAN, a Phase III study in Asian patients, looked at addition of tyrosine kinase inhibitor lapatinib to chemptherapy in advanced HER2 positive gastric cancer. Primary endpoint was Overall Survival (… (full text at CIViC) PMID 24868024 · Satoh et al., 2014 · Open in CIViC | civic |
| Chemotherapy + Pembrolizumab + TrastuzumabCombination | Malignant Gastric Neoplasm | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11251In this randomized, double-blind, placebo-controlled, Phase III trial, 264 patients were enrolled with histologically or cytologically confirmed diagnoses of previously untreated, locally advanced, un… (full text at CIViC) PMID 34912120 · Janjigian et al., 2021 · Open in CIViC | civic |
| 〃 | Gastroesophageal Junction Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11252In this randomized, double-blind, placebo-controlled, Phase III trial, 264 patients were enrolled with histologically or cytologically confirmed diagnoses of previously untreated, locally advanced, un… (full text at CIViC) PMID 34912120 · Janjigian et al., 2021 · Open in CIViC | civic |
| Pertuzumab + TrastuzumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID7302In an updated report of a part of the phase 2a MyPathway trial, 57 patients with treatment-refractory, metastatic colorectal cancer with HER2 amplification received pertuzumab and trastuzumab. Objecti… (full text at CIViC) PMID 30857956 · Meric-Bernstam et al., 2019 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID11668In this clinical study of 38 patients with colorectal cancer (CRC), 28 had CRC with ERBB2 amplification, and were treated with a combination of Pertuzumab and Trastuzumab. The DC rate in the patients … (full text at CIViC) PMID 36315917 · Gupta et al., 2022 · Open in CIViC | civic |
| 〃 | Malignant Biliary Tract NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID5983The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Two of seven… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC | civic |
| 〃 | Malignant Pancreatic Neoplasm | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID5985The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Two of nine … (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC | civic |
| Trastuzumab | Gastric Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1499ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive (overexpression or amplification) advanced gastric cancer, where chemotherapy using fluoropyrimidine-based and plati… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC | civic |
| 〃 | Malignant Gastric Neoplasm | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11253In this open-label, randomized, phase II trial, 187 patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma that had progressed while they were receiving at least two pre… (full text at CIViC) PMID 32469182 · Shitara et al., 2020 · Open in CIViC | civic |
| 〃 | Gastroesophageal Junction Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11254In this open-label, randomized, phase II trial, 187 patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma that had progressed while they were receiving at least two pre… (full text at CIViC) PMID 32469182 · Shitara et al., 2020 · Open in CIViC | civic |
| 〃 | Gastric Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1022ToGA, a Phase III study (NCT01041404) addressed use of trastuzumab in HER2 positive advanced gastric cancer, where chemotherapy using fluoropyrimidine-based and platinum-based combinations had been co… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC | civic |
| Chemotherapy + TrastuzumabCombination | Gastroesophageal Junction Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID11256In this phase 3, open-label, randomized controlled trial, 594 patients (584 in the primary analysis) with HER2-positive amplification or overexpression gastric or gastroesophageal junction adenocarcin… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC | civic |
| Trastuzumab Deruxtecan | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11321In this open-label, phase II trial, 78 patients were enrolled in the study; for the 53 patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 patients (95% C… (full text at CIViC) PMID 33961795 · Siena et al., 2021 · Open in CIViC | civic |
| 〃 | Malignant Gastric Neoplasm | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID7647In a phase 1 trial, 44 patients with HER2-positive gastric or gastroesophageal junction cancer previously treated with trastuzumab were treated with Trastuzumab Deruxtecan (DS-8201a). The response rat… (full text at CIViC) PMID 31047804 · Shitara et al., 2019 · Open in CIViC | civic |
| Trastuzumab Emtansine | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7585In NCI-MATCH, patients with advanced solid tumors other than breast and gastro-esophageal tumors harboring ERBB2 amplification were treated with ad-trastuzumab emtansine (T-DM1). ERBB2 amplification w… (full text at CIViC) PMID 31504139 · Jhaveri et al., 2019 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1689Phase 2 study in 27 patients with HER2 positive (IHC, FISH), KRAS wt metastatic colorectal cancer refractory to standard of care received trastuzumab and lapatinib. After a median follow-up of 94 week… (full text at CIViC) PMID 27108243 · Sartore-Bianchi et al., 2016 · Open in CIViC | civic |
| Pertuzumab + TrastuzumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID5981The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Thirty of 1… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC | civic |
| 〃 | Cholangiocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7638A patient with cholangiocarcinoma harboring with ERBB2 amplification (3+) detected by circulating tumor DNA testing and confirmed by tissue-based testing was treated with trastuzumab and pertuzumab. T… (full text at CIViC) PMID 31453370 · Yarlagadda et al., 2019 · Open in CIViC | civic |