0000000001099310
AUTHOR
Silvia Menendez
Tumor-Associated Fibroblasts Promote HER2-Targeted Therapy Resistance through FGFR2 Activation
AbstractPurpose:Despite the therapeutic success of existing HER2-targeted therapies, tumors invariably relapse. This study aimed at identifying new mechanisms responsible for HER2-targeted therapy resistance.Experimental Design:We have used a platform of HER2-targeted therapy–resistant cell lines and primary cultures of healthy and tumor-associated fibroblasts (TAF) to identify new potential targets related to tumor escape from anti-HER2 therapies.Results:We have shown that TAFs promote resistance to HER2-targeted therapies. TAFs produce and secrete high levels of FGF5, which induces FGFR2 activation in the surrounding breast cancer cells. FGFR2 transactivates HER2 via c-Src, leading to res…
NK Cell Infiltrates and HLA Class I Expression in Primary HER2+ Breast Cancer Predict and Uncouple Pathological Response and Disease-free Survival
Abstract Purpose: We investigated the value of tumor-infiltrating NK (TI-NK) cells and HLA class I tumor expression as biomarkers of response to neoadjuvant anti-HER2 antibody–based treatment in breast cancer. Experimental Design: TI-NK cells and HLA-I were determined by IHC in pretreatment tumor biopsies from two cohorts of patients with HER2-positive breast cancer [discovery cohort (n = 42) and validation cohort (n = 71)]. Tumor-infiltrating lymphocytes (TIL) were scored according to international guidelines. Biomarker association with pathologic complete response (pCR) and disease-free survival (DFS) was adjusted for prognostic factors. Gene set variation analysis was used for determinin…
Preclinical and Clinical Characterization of Fibroblast-derived Neuregulin-1 on Trastuzumab and Pertuzumab Activity in HER2-positive Breast Cancer.
[Purpose]: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab.