| ERBB2 V777L21 |
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| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12103The V777L variant is located in the tyrosine kinase domain. In vitro kinase assays were conducted using recombinant expression of the isolated HER2 kinase domain. In this system wild-type (WT) HER2 sh… (full text at CIViC) PMID 23220880 · Bose et al., 2013 · Open in CIViC | civic |
| 〃 | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID10023A series of HER2 (ERBB2) mutations (G309A, D769H, D769Y, V777L, P780ins, V824I, R678Q, R896C, del755-759, and L755S) were functionally characterized and tested for sensitivity to lapatinib or neratini… (full text at CIViC) PMID 23220880 · Bose et al., 2013 · Open in CIViC | civic |
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11559HPNE 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 |
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID12105To model HER2 missense mutations found in tumors without HER amplification, a targeted gene knock-in method was used to create isogenic MCF-10A and MCF7 human breast epithelial cell lines with a singl… (full text at CIViC) PMID 26508629 · Zabransky et al., 2015 · Open in CIViC | civic |
| 〃 | —UNRESOLVED | Functional | D | Supports Gain Of Function | 2 | submitted | EID12104Wild-type and V777L mutant HER2 proteins were ectopically expressed in NIH3T3 cells. The variant form of HER2 supported anchorage-independent growth in soft agar while the wild-type form did not and … (full text at CIViC) PMID 25720673 · Bellmunt et al., 2015 · Open in CIViC | civic |
| Afatinib | Malignant Breast Neoplasm | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID11690In this phase II NCI-MATCH trial, a patient with ER+ invasive ductal breast cancer with ERBB2 V777L mutation was treated with afatinib. A RECIST response was reported in the patient, however, it wasn'… (full text at CIViC) PMID 35939768 · Bedard et al., 2022 · Open in CIViC | civic |
| Cetuximab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID4452In an in vitro study, NCI-H508 cell lines expressing an ERBB2 V777L mutation demonstrated resistance to cetuximab treatment (IC50 >200 ug/ml) compared to NCI-H508 cells expressing ERBB2 wild-type (IC5… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC | civic |
| Everolimus + LapatinibCombination | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID13332T4D7 and MCf7 breast cancer cells expressing V777L were sensitive to lapatinib, everolimus and the combination of lapatinib + everolimus in colony formation assays and three-dimensional culture in Ma… (full text at CIViC) PMID 35523006 · Ma et al., 2022 · Open in CIViC | civic |
| Fulvestrant | Malignant Breast Neoplasm | Predictive | D | Supports Resistance | 3 | submitted | EID13334T47D and MCF7 breast cancer cells expressing V777L were no longer dependent on estrogen for cell viability in vitro and were resistant to treatment with fulvestrant in cell viability assays. T47D cel… (full text at CIViC) PMID 30531871 · Nayar et al., 2019 · Open in CIViC | civic |
| Lapatinib | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID9697Ba/F3 cells expressing ERBB2 V777L were treated with lapatinib and showed an IC50 value of 27nM, compared to 30nM for wild-type ERBB2 cells. The authors considered V777L as lapatinib-sensitive. PMID 22046346 · Kancha et al., 2011 · Open in CIViC | civic |
| Neratinib | Malignant NeoplasmALIAS | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID12106In the SUMMIT basket trial (NCT01953926) patients with solid tumors of various histologies harboring mutations of either HER2 or HER3 were enrolled and treated with the pan-HER kinase inhibitor nerati… (full text at CIViC) PMID 29420467 · Hyman et al., 2018 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 5 | accepted | EID288In MCF10A cell lines, the V777L mutation was shown to be sensitive to neratinib. PMID 23220880 · Bose et al., 2013 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13333T47D and MCF7 breast cancer cells expressing V777L were sensitive to treatment with neratinib, a tyrosine kinase inhibitor, in cell viability assays. PMID 30531871 · Nayar et al., 2019 · Open in CIViC | civic |
| 〃 | Pancreatic Ductal Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11569Neratinib suppresses anchorage-independent growth in transduced HPNE cells with the variant in a concentration-dependent manner (Figure 6B–C) with complete inhibition at a concentration of 0.5 µM (Fig… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| Afatinib + Lapatinib + Neratinib + OsimertinibSubstitutes | Malignant NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12101Ba/F3 mouse lymphoid cells expressing wild-type or V777L mutant HER2 were treated with afatinib, neratinib, osimertinib or DMSO (vehicle) for 72 hours, at which time viable cells were measured using t… (full text at CIViC) PMID 29967253 · Nagano et al., 2018 · Open in CIViC | civic |
| Fulvestrant + NeratinibCombination | Malignant Breast Neoplasm | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID13336One patient with with metastatic breast cancer harboring V777L did not respond to treatment with letrozole plus palbociclib but experienced a partial response to neratinib plus fulvestrant. PMID 30531871 · Nayar et al., 2019 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13337Genomic information indicates that V777L is more prevalent in metastatic breast cancers following endocrine therapy. In cell proliferation assays, MCF7 breast epithelial cells expressing V777L were no… (full text at CIViC) PMID 30314968 · Croessmann et al., 2019 · Open in CIViC | civic |
| Palbociclib | Malignant Breast Neoplasm | Predictive | D | Supports Resistance | 3 | submitted | EID13335T47D breast cancer cells expressing V777L were resistant to the CDK4 and CDK6 inhibitor palbociclib, both alone and in combination with fulvestrant, in cell viability assays. PMID 30531871 · Nayar et al., 2019 · Open in CIViC | civic |
| Trastuzumab | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID12102Ba/F3 mouse lymphoid cells expressing wild-type or V777L mutant HER2 were treated with afatinib, neratinib, osimertinib or DMSO (vehicle) for 72 hours, at which time viable cells were measured using t… (full text at CIViC) PMID 29967253 · Nagano et al., 2018 · Open in CIViC | civic |
| Lapatinib + Neratinib + TrastuzumabCombination | Malignant Colon Neoplasm | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1177Colon cancer patient derived xenografts with HER2 mutations are sensitive to HER2 targeted drugs and the greatest tumor reduction was seen with the combination of a tyrosine kinase inhibitor with tras… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC | civic |
| Trastuzumab + Trastuzumab EmtansineSubstitutes | HER2-Positive Breast CarcinomaALIAS | Predictive | C | Supports Resistance | 3 | submitted | EID5817In a cohort of 205 Her2-receptor amplified breast cancers, 20 experienced recurrence after trastuzumab therapy. Of the 20 recurrent cases, only six patients had metastatic sites, excluding brain metas… (full text at CIViC) PMID 27900589 · Hirotsu et al., 2017 · Open in CIViC | civic |