Abonnement à la biblothèque: Guest
Portail numérique Bibliothèque numérique eBooks Revues Références et comptes rendus Collections
Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN Imprimer: 0893-9675
ISSN En ligne: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v17.i1.20
pages 1-16

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

Brent N. Rexer
Departments of Medicine and Cancer Biology; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center; Vanderbilt University School of Medicine, Nashville, TN
Carlos L. Arteaga
Departments of Medicine and Cancer Biology; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center; Vanderbilt University School of Medicine, Nashville, TN

RÉSUMÉ

Approximately 25% of human breast cancers overexpress the HER2 (ErbB2) proto-oncogene, which confers a more aggressive tumor phenotype and associates with a poor prognosis in patients with this disease. Two approved therapies targeting HER2, the monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib, are clinically active against this type of breast cancer. However, a significant fraction of patients with HER2+ breast cancer treated with these agents eventually relapse or develop progressive disease. This suggests that tumors acquire or possess intrinsic mechanisms of resistance that allow escape from HER2 inhibition. This review focuses on mechanisms of intrinsic and/or acquired resistance to HER2-targeted therapies that have been identified in preclinical and clinical studies. These mechanisms involve alterations to HER2 itself, coexpression or acquisition of bypass signaling through other receptor or intracellular signaling pathways, defects in mechanisms of cell cycle regulation or apoptosis, and host factors that may modulate drug response. Emerging clinical evidence already suggests that combinations of therapies targeting HER2 as well as these resistance pathways will be effective in overcoming or preventing resistance.


Articles with similar content:

Epidermal Growth Factor Receptor Tyrosine Kinase: A Potential Target in Treatment of Non-Small-Cell Lung Carcinoma
Journal of Environmental Pathology, Toxicology and Oncology, Vol.36, 2017, issue 2
Vinod Prabhu, Venugopal Vinod Prabhu
Molecular Mechanisms Underlying the Role of MicroRNAs in Resistance to Epidermal Growth Factor Receptor-Targeted Agents and Novel Therapeutic Strategies for Treatment of Non-Small-Cell Lung Cancer
Critical Reviews™ in Oncogenesis, Vol.18, 2013, issue 4
Elena Galvani, Godefridus J. Peters, Mina Maftouh, Elisa Giovannetti, Amir Avan
Immune Responses to BRAF-Targeted Therapy in Melanoma: Is Targeted Therapy Immunotherapy?
Critical Reviews™ in Oncogenesis, Vol.21, 2016, issue 1-2
Mark C. Kelley
The Antitumor Cytotoxic Response: If the Killer Cells Play the Music, the Microenvironmental Hypoxia Plays the Tune
Critical Reviews™ in Immunology, Vol.40, 2020, issue 2
Salem Chouaib
Roles Each of Snail, Yin Yang 1, and RKIP in the Regulation of Tumor Cells Chemo- Immuno-Resistance to Apoptosis
Onco Therapeutics, Vol.4, 2013, issue 1
Sara Huerta-Yepez, Mario I. Vega, Ali R. Jazirehi, Stavroula Baritaki, Benjamin Bonavida