Abstract B36: Inhibition of the autocrine IL-6-JAK2-STAT3-Calprotectin axis as targeted therapy for HR-/HER2+ breast cancers

Although, HER2+ tumors are commonly considered as a single entity, there is increasing evidence indicating that important intrinsic differences associated to hormone receptor status (HR) exist. Each of the two groups, HR+ and HR-, represent about 1/2 of all HER2+ breast cancers.Compared to HR+/HER2+, HR-/HER2+ tumors present worst histopathological characteristics. HR+/HER2+ tumors preferentially recur in bone while there is a strong trend for more visceral metastases in the HR-/HER2+ cancers. Moreover, despite a higher rate of pathologic complete responses (pCR) to neoadjuvant chemotherapy HR-/HER2+ patients still have an increased risk of death within five years of diagnosis. Intrinsic differences between HR-/HER2+ and HR+/HER2+ breast cancers are also found at the molecular level, as highlighted by unsupervised cluster analysis of gene expression profiles. The latter clear identifies two distinct HER2+ subtypes. Most tumors clinically classified as HR+/HER2+ fall in the luminal B subtype, while most HR-/HER2+ are part of the HER2 enriched subtype.Indeed, while HR+/HER2+ patients benefit from anti-hormonal and HER2 targeted therapies, the outcome of HR-/HER2+ patients strongly depends on their response to chemotherapy as well as anti-HER2 therapy. Thus, to identify genes that represent novel mechanistic dependencies in HR-/HER2+ breast cancer cells, we designed an integrative approach that combines functional genomic (RNAi screens) and computational algorithms.Our integrati...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research