Targeting MAPK and PI3K signaling via CK2 inhibition in acral melanoma

Successful treatment for advanced acral melanoma occurring on the palms, soles and nail bed, is a tremendous challenge. This form of melanoma is different from cutaneous melanoma that arises in hair-bearing sites not only because of the location, but also the genetic composition and clinical behavior. Acral melanomas are more aggressive and have poorer prognosis, especially because they tend to be more advanced at presentation. This type of melanoma is also characterized by a poor response to current therapeutic approaches with targeted therapies and immunotherapies. Thus, there is an extreme need for rational development of therapeutic strategies to overcome the poor prognosis of acral melanoma. Here, we will investigate the mechanisms and potential therapeutic benefits of treating acral melanomas with CK2 inhibitors to target cell signaling pathways that are crucial for tumor cell proliferation and immune suppressive processes, in combination with currently in-use therapies to improve the therapeutic outcomes. We postulate that an additional benefit of our proposed combination therapy will be preventing resistance to other targeted therapies increasing their efficacy. This innovative combination therapeutic strategy to increase clinical success makes use of clinically available drugs, and therefore offers the possibility for near-term translation to the clinic to ultimately extend survival and provide a better quality of life of patients with acral melanoma.