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Ref Type Journal Article
PMID (30449325)
Authors Pahuja KB, Nguyen TT, Jaiswal BS, Prabhash K, Thaker TM, Senger K, Chaudhuri S, Kljavin NM, Antony A, Phalke S, Kumar P, Mravic M, Stawiski EW, Vargas D, Durinck S, Gupta R, Khanna-Gupta A, Trabucco SE, Sokol ES, Hartmaier RJ, Singh A, Chougule A, Trivedi V, Dutt A, Patil V, Joshi A, Noronha V, Ziai J, Banavali SD, Ramprasad V, DeGrado WF, Bueno R, Jura N, Seshagiri S
Title Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations.
Journal Cancer cell
Vol 34
Issue 5
Date 2018 11 12
URL
Abstract Text Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L. Using a saturation mutagenesis screen and testing of patient-derived mutations we found several activating TMD and JMD mutations. Structural modeling and analysis showed that the TMD/JMD mutations function by improving the active dimer interface or stabilizing an activating conformation. Further, we found that HER2 G660D employed asymmetric kinase dimerization for activation and signaling. Importantly, anti-HER2 antibodies and small-molecule kinase inhibitors blocked the activity of TMD/JMD mutants. Consistent with this, a G660D germline mutant lung cancer patient showed remarkable clinical response to HER2 blockade.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ERBB2 E693K missense gain of function - predicted ERBB2 (HER2) E693K lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). E693K results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
ERBB2 G660D missense gain of function ERBB2 (HER2) G660D lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). G660D leads to constitutive activation of Erbb2 (Her2) and increased downstream signaling in cell culture (PMID: 26545934) and results in increased cell survival and the formation of multi-acinar bodies in the absence of ligand (PMID: 30449325).
ERBB2 G660R missense gain of function ERBB2 (HER2) G660R lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). G660R results in elevated Erbb2 (Her2) phosphorylation in vitro and increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325).
ERBB2 K676R missense no effect ERBB2 (HER2) K676R lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). K676R confers no effect to the Erbb2 (Her2) protein, resulting in kinase activity, phosphorylation, and cell morphology in culture similar to wild-type (PMID: 27697991).
ERBB2 K681N missense unknown ERBB2 (HER2) K681N lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). K681N has been identified in sequencing studies (PMID: 28164408), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Jul 2020).
ERBB2 L663P missense unknown ERBB2 (HER2) L663P lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). L663P is conflicting as it results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) in one study (PMID: 29533785), but in another study when expressed in cells in the presence of wild-type Erbb2 (Her2), it results in large multi-acinar bodies and increased cell survival as compared to wild-type in culture (PMID: 30449325), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
ERBB2 P702L missense unknown ERBB2 (HER2) P702L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). P702L has been identified in the scientific literature (PMID: 31685261, PMID: 30449325), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Jul 2020).
ERBB2 Q679L missense gain of function ERBB2 (HER2) Q679L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q679L confers a gain of function to the Erbb2 (Her2) protein as indicated by increased phosphorylation of Erbb2 (Her2), downstream signaling, and colony formation, and is transforming in cell culture (PMID: 31046123).
ERBB2 Q680R missense no effect ERBB2 (HER2) Q680R lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q680R confers no effect to the Erbb2 (Her2) protein, resulting in kinase activity, phosphorylation, and cell morphology in culture similar to wild-type (PMID: 27697991).
ERBB2 Q709L missense gain of function ERBB2 (HER2) Q709L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q709L results in increased cell survival in the presence of wild-type Erbb2 (Her2) and demonstrates elevated Erbb2 (Her2) phosphorylation compared to wild-type Erbb2 (Her2) in vitro and the formation of large multi-acinar bodies in culture, both in the presence and absence of wild-type Erbb2 (Her2) (PMID: 30449325).
ERBB2 Q711H missense no effect - predicted ERBB2 (HER2) Q711H lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q711H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
ERBB2 R677L missense gain of function - predicted ERBB2 (HER2) R677L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R677L results in increased cell survival as compared wild-type Erbb2 (Her2) in culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
ERBB2 R678L missense unknown ERBB2 (HER2) R678L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R678L has been identified in the scientific literature (PMID: 25636205), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2020).
ERBB2 R678Q missense unknown ERBB2 (HER2) R678Q lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). The functional effect of R678Q is conflicting, as it demonstrates phosphorylation levels and transformation potential comparable to wild-type Erbb2 (Her2) protein in cell culture and xenograft models (PMID: 29533785, PMID: 23220880), however, in other studies, results in increased phosphorylation of Erbb2 (Her2) and activation of downstream signaling (PMID: 24971884), and is transforming in culture (PMID: 30449325, PMID: 31588020). Y
ERBB2 R678W missense gain of function - predicted ERBB2 (HER2) R678W lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R678W results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
ERBB2 R683Q missense no effect - predicted ERBB2 (HER2) R683Q lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R683Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
ERBB2 S653C missense gain of function ERBB2 (HER2) S653C lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). S653C results in constitutive activation of Erbb2 (Her2) and phosphorylation of Shc and Erk in cell culture (PMID: 24971884) and leads to increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325).
ERBB2 S656C missense gain of function - predicted ERBB2 (HER2) S656C lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). S656C results in increased cell survival as compared to wild-type Erbb2 (Her2) in cell culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
ERBB2 T686A missense gain of function - predicted ERBB2 (HER2) T686A lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). T686A results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
ERBB2 T686M missense no effect - predicted ERBB2 (HER2) T686M lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). T686M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
ERBB2 V659E missense gain of function ERBB2 (HER2) V659E lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). V659E results in constitutive phosphorylation of Erbb2 (Her2), activation of Src and Akt signaling in cell culture, and increased tumor metastasis in animal models (PMID: 16489002, PMID: 15753384), and leads to increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325), and in one of two cell lines, V659E increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) (PMID: 29533785).
ERBB2 V697L missense unknown ERBB2 (HER2) V697L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). V697L has been identified in the scientific literature (PMID: 29247016, PMID: 28679771), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2020).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 L663P Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor sensitive Trastuzumab Preclinical Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D treated with Herceptin (trastuzumab) demonstrated decreased proliferation, reduced survival, and inhibition of colony formation in culture, and in mouse models led to improved survival compared to control models with wild-type ERBB2 (HER2) (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor predicted - sensitive Pertuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated decreased cell proliferation and reduced survival when treated with Perjeta (pertuzumab) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor predicted - sensitive Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated decreased cell proliferation and reduced survival when treated with Herceptin (trastuzumab) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - resistant Pertuzumab Preclinical - Cell culture Actionable In a preclinical study, treatment with Perjeta (pertuzumab) in transformed cells expressing ERBB2 (HER2) G660R was not effective in inhibiting cell proliferation and survival as compared to other activating ERBB2 (HER2) mutations in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R demonstrated decreased cell proliferation and reduced survival when treated with Nerlynx (neratinib) in culture (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E demonstrated decreased cell proliferation and reduced survival when treated with Nerlynx (neratinib) in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - sensitive Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R demonstrated decreased cell proliferation and reduced survival when treated with Herceptin (trastuzumab) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor predicted - sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q demonstrated decreased cell proliferation and reduced survival when treated with Nerlynx (neratinib) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor predicted - sensitive Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q demonstrated decreased cell proliferation and reduced survival when treated with Herceptin (trastuzumab) in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor predicted - sensitive Pertuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L demonstrated decreased cell proliferation and reduced survival when treated with Perjeta (pertuzumab) in culture (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor predicted - sensitive Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L demonstrated decreased cell proliferation and reduced survival when treated with Herceptin (trastuzumab) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor predicted - sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated decreased cell proliferation and reduced survival when treated with Nerlynx (neratinib) in culture (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 Q709L Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Q709L demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - sensitive Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E demonstrated decreased cell proliferation and reduced survival when treated with Herceptin (trastuzumab) in culture (PMID: 30449325). 30449325
ERBB2 L663P Advanced Solid Tumor predicted - resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L663P demonstrated resistance to treatment with Erbitux (cetuximab) in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor predicted - sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D demonstrated decreased cell proliferation and reduced survival when treated with Nerlynx (neratinib) in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor predicted - resistant Pertuzumab Preclinical - Cell culture Actionable In a preclinical study, treatment with Perjeta (pertuzumab) led to induced growth and colony formation of cells expressing ERBB2 (HER2) G660D in culture (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor predicted - sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D demonstrated decreased cell proliferation and reduced survival when treated with Tykerb (lapatinib) in culture (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 G660D lung cancer sensitive Afatinib Case Reports/Case Series Actionable In a clinical study, a patient with lung cancer harboring a germline mutation, ERBB2 (HER2) G660D, demonstrated improved symptoms within 30 days of Gilotrif (afatinib) treatment, as well as a 21% reduction in tumor volume in 12 weeks and a durable response that lasted for more than 15 weeks (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 R678Q Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) R678Q demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 G660R Advanced Solid Tumor no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660R did not benefit from treatment with Iressa (gefitinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor no benefit Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V659E did not benefit from treatment with Tarceva (erlotinib) in culture when compared to Erbb2 (Her2) inhibitors (PMID: 30449325). 30449325
ERBB2 G660D Advanced Solid Tumor predicted - sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G660D demonstrated decreased cell proliferation and reduced survival when treated with Gilotrif (afatinib) in culture (PMID: 30449325). 30449325
ERBB2 V659E Advanced Solid Tumor predicted - resistant Pertuzumab Preclinical - Cell culture Actionable In a preclinical study, treatment with Perjeta (pertuzumab) led to induced growth of cells expressing ERBB2 (HER2) V659E in culture (PMID: 30449325). 30449325