Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer

摘要: // Debora de Melo Gagliato 1 , Denis Leonardo Fontes Jardim Mario Sergio Pereira Marchesi 2 and Gabriel N. Hortobagyi 3 Centro Oncologia do Parana, Curitiba SP, Brazil Roche Pharmaceuticals, Sao Paulo The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Gagliato, email: Keywords : breast cancer, HER2 disease, trastuzumab, anti-HER2 therapy, resistance to treatment Received September 08, 2015 Accepted January 18, 2016 Published 27, Abstract Breast (BC) is a highly prevalent disease. A woman living in the United States has 12.3% lifetime risk being diagnosed with cancer [ ]. It most common female second cause death women Of note, amplification or overexpression Human Epidermal Receptor (HER2) oncogene present approximately 18 20% primary invasive cancers, until personalized therapy became available for this specific BC subtype, worst rates Overall Survival (OS) Recurrence-Free (RFS) were observed HER2+ cohort, compared all other types, including triple negative (TNBC) member epidermal growth factor receptor (EGFR) family. Other family members include EGFR HER1, HER3 HER4. can form heterodimers any three receptors, considered be preferred dimerization partner HER ErbB receptors 4 Phosphorylation tyrosine residues within cytoplasmic domain result culminates into initiation variety signalling pathways involved cellular proliferation, transcription, motility apoptosis inhibition 5 In addition an important prognostic BC, also identifies those patients who benefit from agents that target HER2, such as pertuzumab, trastuzumab emtansine (T-DM1) small molecules kinase inhibitors 6 11 127 ].In fact, altered natural history both early metastatic disease setting, major way 8 - 10 Nevertheless, there are many will eventually develop despite treated setting. Moreover, advanced tumors may reach point where no achieve control, recently approved drugs, T-DM1. This review paper concentrate on biological ultimately lead therapies summarizing their mechanisms. Strategies overcome resistance, rationale each tactics revert scenario presented reader.