Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Abstract

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Extramammary Paget’s disease (EMPD) is a rare, slow-growing, cutaneous adenocarcinoma that usually originates in the anogenital area and axillae outside the mammary glands. EMPD mostly progresses slowly and is often diagnosed as carcinoma in situ; however, upon becoming invasive, it promptly and frequently metastasizes to regional lymph nodes, leading to subsequent distant metastasis. To date, several chemotherapy regimens have been used to treat metastatic EMPD; however, they present limited effect and patients with distant metastasis exhibit a poor prognosis. Recently, basic and translational investigative research has elucidated factors and molecular mechanisms underlying the promotion of metastasis, which can lead to targeted therapy-based emerging treatment strategies. Here, we aim to discuss current therapies and their limitations; advancements in illustrating mechanisms promoting invasion, migration, and proliferation of EMPD tumor cells; and future therapeutic approaches for metastatic EMPD that may enhance clinical outcomes.

Keywords

• metastatic extramammary Paget’s disease
• HER2–PI3K/ERK signaling
• lymphangiogenesis
• CXCR4–stromal cell-derived factor-1 axis
• CD163+M2 macrophage
• receptor activator of nuclear factor kappa-B ligand–RANK signaling