Abstract ES7-3: ES7-3 Mechanisms of resistance to Her2 positive disease

The epidermal growth factor receptor-2 (HER2) is a member of the HER family, a robust and complex signaling network with multiple redundant inputs (ligands and receptors), central signals, and ample feedback routes. HER2 amplification occurs in about 15% of breast cancers and is a major driver of cell proliferation and survival. Therapies targeting HER2, including the monoclonal antibodies trastuzumab and pertuzumab, the trastuzumab drug conjugate T-DM1, and the HER1/2 tyrosine kinase inhibitor lapatinib, have substantially improved outcome of patients with this subtype of disease. Stemming from preclinical evidence, in recent years the use of combined (dual) anti-HER agents to more completely block the receptor layer (HER1, 2, and 3), has been successfully translated to the clinic, and the latest studies suggest that at least some oncogene-addicted HER2-positive tumors might not require chemotherapy at all if HER2 is effectively blocked. Experimental and clinical findings further propose that blocking estrogen receptor would also be necessary in tumors expressing both receptors. Yet, despite progress in the care of HER2-positive breast cancer, treatment resistance remains a key problem in many patients. Therefore, establishing molecular determinants of response and resistance and associated biomarkers is essential in order to empower the identification of patients who may benefit from a de-escalation approach of only receptor-targeted therapy without chemotherapy. We also ne...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Invited Speaker Abstracts Source Type: research