Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications

Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu Oncogene

1987 • 11,429 citations

Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

2001 • 11,070 citations

Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer

1989 • 6,734 citations

Untangling the ErbB signalling network

2001 • 6,623 citations

Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer

2005 • 5,199 citations

Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer

2005 • 4,901 citations

PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

1997 • 4,753 citations

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

2007 • 4,320 citations

EGFRMutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib

2005 • 3,807 citations

Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain

2005 • 3,450 citations

Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer

2006 • 3,283 citations

Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets

2000 • 2,694 citations

PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients

2004 • 1,810 citations

A Functional Genetic Approach Identifies the PI3K Pathway as a Major Determinant of Trastuzumab Resistance in Breast Cancer

2007 • 1,562 citations

Adjuvant Docetaxel or Vinorelbine with or without Trastuzumab for Breast Cancer

2006 • 1,404 citations

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer

2007 • 1,234 citations

Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex

2004 • 1,052 citations

Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3

2007 • 941 citations

Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer

2010 • 938 citations

Immunoglobulin G Fragment C Receptor Polymorphisms and Clinical Efficacy of Trastuzumab-Based Therapy in Patients With HER-2/neu–Positive Metastatic Breast Cancer

2008 • 936 citations

Mutation of the PIK3CA Gene in Ovarian and Breast Cancer

2004 • 898 citations

Activity of the Dual Kinase Inhibitor Lapatinib (GW572016) against HER-2-Overexpressing and Trastuzumab-Treated Breast Cancer Cells

2006 • 897 citations

Insulin-Like Growth Factor-I Receptor Signaling and Resistance to Trastuzumab (Herceptin)

2001 • 868 citations

Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas

1995 • 831 citations

PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma

2005 • 831 citations

Expression of p95HER2, a Truncated Form of the HER2 Receptor, and Response to Anti-HER2 Therapies in Breast Cancer

2007 • 825 citations

Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941

2009 • 789 citations

Insulin-like Growth Factor-I Receptor/Human Epidermal Growth Factor Receptor 2 Heterodimerization Contributes to Trastuzumab Resistance of Breast Cancer Cells

2005 • 761 citations

NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations

2008 • 757 citations

Intragenic ERBB2 kinase mutations in tumours

2004 • 753 citations

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

2010 • 723 citations

Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study

2009 • 657 citations

Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways

2002 • 656 citations

The PIK3CA gene is mutated with high frequency in human breast cancers

2004 • 654 citations

Somatic Mutations of the HER2 Kinase Domain in Lung Adenocarcinomas

2005 • 652 citations

Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy

2010 • 624 citations

Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action.

2002 • 607 citations

A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

2008 • 595 citations

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

2009 • 584 citations

Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib

2006 • 579 citations

Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer

2010 • 572 citations

Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo.

2001 • 550 citations

Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas.

1995 • 546 citations

The Therapeutic Effect of Anti-HER2/neu Antibody Depends on Both Innate and Adaptive Immunity

2010 • 533 citations

Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways

2011 • 500 citations

Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer

2010 • 498 citations

Decreased Accessibility and Lack of Activation of ErbB2 in JIMT-1, a Herceptin-Resistant, MUC4-Expressing Breast Cancer Cell Line

2005 • 494 citations

Pilot Study of the Mechanism of Action of Preoperative Trastuzumab in Patients with Primary Operable Breast Tumors Overexpressing HER2

2004 • 494 citations

Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235

2008 • 485 citations

Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer

2010 • 477 citations

Human Breast Cancer Cells Selected for Resistance to Trastuzumab In vivo Overexpress Epidermal Growth Factor Receptor and ErbB Ligands and Remain Dependent on the ErbB Receptor Network

2007 • 474 citations

Novel Mechanism of Lapatinib Resistance in HER2-Positive Breast Tumor Cells: Activation of AXL

2009 • 462 citations

Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer

2006 • 457 citations

HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors

2006 • 449 citations

Evidence that Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor that Inhibits PI3K Signaling

2009 • 442 citations

Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase

2011 • 425 citations

Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells

2008 • 415 citations

Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3.

1995 • 407 citations

A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer

2006 • 369 citations

Study of the Biologic Effects of Lapatinib, a Reversible Inhibitor of ErbB1 and ErbB2 Tyrosine Kinases, on Tumor Growth and Survival Pathways in Patients With Advanced Malignancies

2005 • 366 citations

A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient

2004 • 324 citations

Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib

2010 • 313 citations

Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab

2005 • 313 citations

Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition

2009 • 312 citations

ErbB2 Potentiates Breast Tumor Proliferation through Modulation of p27^Kip1-Cdk2 Complex Formation: Receptor Overexpression Does Not Determine Growth Dependency

2000 • 304 citations

Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2 ⁺ breast cancer patients

2011 • 303 citations

P27kip1 Down-Regulation Is Associated with Trastuzumab Resistance in Breast Cancer Cells

2004 • 293 citations

PTEN, PIK3CA, p-AKT, and p-p70S6K Status

2010 • 283 citations

BIM Expression in Treatment-Naïve Cancers Predicts Responsiveness to Kinase Inhibitors

2011 • 274 citations

Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling

2007 • 256 citations

The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides.

2002 • 248 citations

Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer

2007 • 244 citations

Neoadjuvant Trastuzumab Induces Apoptosis in Primary Breast Cancers

2005 • 239 citations

Loss of Phosphatase and Tensin Homolog or Phosphoinositol-3 Kinase Activation and Response to Trastuzumab or Lapatinib in Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancers

2010 • 237 citations

Heterotrimerization of the Growth Factor Receptors erbB2, erbB3, and Insulin-like Growth Factor-I Receptor in Breast Cancer Cells Resistant to Herceptin

2010 • 231 citations

Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2

2007 • 221 citations

Somatic Mutations of ERBB2 Kinase Domain in Gastric, Colorectal, and Breast Carcinomas

2006 • 220 citations

Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation

2006 • 209 citations

Elevation of Receptor Tyrosine Kinase EphA2 Mediates Resistance to Trastuzumab Therapy

2009 • 203 citations

Rat Muc4 (sialomucin complex) reduces binding of anti‐ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance

2002 • 200 citations

Preclinical Testing of Clinically Applicable Strategies for Overcoming Trastuzumab Resistance Caused by PTEN Deficiency

2007 • 196 citations

An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance

2009 • 185 citations

Trastuzumab beyond progression: Overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer

2011 • 183 citations

Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: Mutations are mainly present in adenocarcinomas with bronchioloalveolar features

2006 • 175 citations

HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer

2008 • 169 citations

Resiliency and Vulnerability in the HER2-HER3 Tumorigenic Driver

2010 • 168 citations

Transforming Growth Factor β Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab

2008 • 161 citations

Lapatinib Antitumor Activity Is Not Dependent upon Phosphatase and Tensin Homologue Deleted on Chromosome 10 in ErbB2-Overexpressing Breast Cancers

2007 • 146 citations

Clinical Benefit of Lapatinib-Based Therapy in Patients with Human Epidermal Growth Factor Receptor 2–Positive Breast Tumors Coexpressing the Truncated p95HER2 Receptor

2010 • 145 citations

Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions

2011 • 139 citations

Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition

2011 • 139 citations

A novel splice variant ofHER2 with increased transformation activity

1998 • 130 citations

Role of exon-16-deleted HER2 in breast carcinomas

2006 • 128 citations

Patterns of EGFR, HER2, TP53, and KRAS Mutations of p14arf Expression in Non–Small Cell Lung Cancers in Relation to Smoking History

2007 • 106 citations

Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck

2006 • 99 citations

Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells

2010 • 98 citations

H1047R phosphatidylinositol 3-kinase mutant enhances HER2-mediated transformation by heregulin production and activation of HER3

2010 • 97 citations

MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells

2009 • 91 citations

Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein.

2003 • 89 citations

A Minimal Fragment of MUC1 Mediates Growth of Cancer Cells

2008 • 77 citations

MUC1* Mediates the Growth of Human Pluripotent Stem Cells

2008 • 73 citations

Genes Affecting the Cell Cycle, Growth, Maintenance, and Drug Sensitivity Are Preferentially Regulated by Anti-HER2 Antibody through Phosphatidylinositol 3-Kinase-AKT Signaling

2004 • 70 citations

Roles of BIM induction and survivin downregulation in lapatinib-induced apoptosis in breast cancer cells with HER2 amplification

2011 • 69 citations

ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines

2007 • 66 citations

A novel interaction between HER2/neu and cyclin E in breast cancer

2010 • 64 citations

Detection of epidermal growth factor receptor and human epidermal growth factor receptor 2 activating mutations in lung adenocarcinoma by high-resolution melting amplicon analysis: correlation with gene copy number, protein expression, and hormone receptor expression

2006 • 61 citations

HER2-positive breast cancer cells resistant to trastuzumab and lapatinib lose reliance upon HER2 and are sensitive to the multitargeted kinase inhibitor sorafenib

2010 • 49 citations

Insulin-like growth factor-1 receptor (IGF-1R) expression does not predict for resistance to trastuzumab-based treatment in patients with Her-2/neu overexpressing metastatic breast cancer

2005 • 49 citations

Inhibitor of Apoptosis (IAP) survivin is indispensable for survival of HER2 gene-amplified breast cancer cells with primary resistance to HER1/2-targeted therapies

2011 • 48 citations

Truncated ErbB2 Expressed in Tumor Cell Nuclei Contributes to Acquired Therapeutic Resistance to ErbB2 Kinase Inhibitors

2011 • 46 citations

Direct resequencing of the completeERBB2coding sequence reveals an absence of activating mutations inERBB2amplified breast cancer

2008 • 11 citations