Abstract
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been implicated in the pathogenesis of a variety of neoplasms. As suggested by its name, ALK was first described as part of a translocation product in cases of anaplastic large-cell lymphoma, with other genetic and cytogenetic ALK mutations subsequently coming to attention in the development of many other hematologic and solid organ malignancies. ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma. The characterization of ALK-positivity in these cutaneous malignancies presents exciting opportunities for utilizing ALK-targeted inhibitors in the treatment of these diseases.
Highlights
In the last two decades, new genetic and cytogenetic mutations in the tyrosine kinase, anaplastic lymphoma kinase (ALK), have been implicated in the pathogenesis of several neoplasms
This article will explore the role of Anaplastic lymphoma kinase (ALK) mutations in cutaneous malignancies, including its well-known association with systemic and primary cutaneous anaplastic large-cell lymphoma (ALCL), as well as its emerging role in other cutaneous malignancies, such as melanoma, spitzoid melanocytic neoplasms, epithelioid fibrous histiocytomas, Merkel cell carcinoma, and basal cell carcinoma
These findings offer hope for additional insights into the characterization of processes leading to secondary cutaneous involvement and properties for targeted therapy to address skin involvement in cases of ALK-positive systemic ALCL
Summary
In the last two decades, new genetic and cytogenetic mutations in the tyrosine kinase, anaplastic lymphoma kinase (ALK), have been implicated in the pathogenesis of several neoplasms. This article will explore the role of ALK mutations in cutaneous malignancies, including its well-known association with systemic and primary cutaneous ALCL, as well as its emerging role in other cutaneous malignancies, such as melanoma, spitzoid melanocytic neoplasms, epithelioid fibrous histiocytomas, Merkel cell carcinoma, and basal cell carcinoma. The article will summarize the role of ALK in disease pathogenesis, as well as current efforts to develop ALK-targeted cancer therapies for these malignancies
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