The hedgehog pathway in triple-negative breast cancer

Abstract

Treatment of triple-negative breast cancer (TNBC) remains challenging due to the underlying heterogeneity of this disease coupled with the lack of predictive biomarkers and effective targeted therapies. Intratumoral heterogeneity, particularly enrichment for breast cancer stem cell-like subpopulations, has emerged as a leading hypothesis for systemic therapy resistance and clinically aggressive course of poor prognosis TNBC. A growing body of literature supports the role of the stem cell renewal Hedgehog (Hh) pathway in breast cancer. Emerging preclinical data also implicate Hh signaling in TNBC pathogenesis. Herein, we review the evidence for a pathophysiologic role of Hh signaling in TNBC and explore mechanisms of crosstalk between the Hh pathway and other key signaling networks as well as their potential implications for Hh-targeted interventions in TNBC.

Given the increasingly recognized role of aberrant Hedgehog signaling in breast tumorigenesis as a whole and TNBC in particular, we sought to review all relevant preclinical data and provide a concise summary of the mechanisms of Hedgehog signaling in this breast cancer subtype. Further, we extend our review to recent findings of both established and potential crosstalk with other key signaling pathways which may potentially impact the efficacy of agents targeting the Hedgehog pathway in TNBC.

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