Current treatments and emerging therapies of human polyomavirus‐associated skin diseases: a comprehensive review

Abstract

Since Merkel cell polyomavirus (MCPyV) was linked as the predominant etiology of Merkel cell carcinoma (MCC) in 2008, three additional human polyomaviruses (HPyV) have been definitively linked to cutaneous diseases—trichodysplasia spinulosa virus (TSPyV) and human polyomavirus 6 and 7 (HPyV6, HPyV7). TSPyV contributes to the development of trichodysplasia spinulosa (TS), and HPyV6/7 is associated closely with the eruption of pruritic and dyskeratotic dermatoses (PDD). Clinically, MCC is treated with surgical excision and radiation with adjuvant chemotherapy, although newer treatment options include immune checkpoint inhibition. These novel immunotherapies hold promise for the treatment of metastatic MCC, but resistance and side effects prevent a significant proportion of patients from realizing their benefits. Based on previous case reports, the standard of care for the less deadly but disfiguring cutaneous disease TS include immunosuppressant (IS) reduction, the use of antivirals such as cidofovir (CDV) or valganciclovir (VGCV), or a combination of these treatments. Similar treatments were attempted for PDD, but oral acitretin was found to be most effective. As MCC, TS, and PDD are rare diseases, further research is required for effective treatments. In this review, we summarize clinical trials, preclinical studies, and case reports that present outcomes and side effects of current and emerging treatments for HPyV‐associated cutaneous diseases, offering a comprehensive resource for clinical application and prospective clinical trials.

Selinexor targets expression of metabolic genes in Merkel cell carcinoma cells

“…21,22 Selinexor was observed to decrease MCPyV-positive MCC cell proliferation by targeting the viral small T and large T antigens. 2,14,23,24 Selinexor was previously tested on MCPyV-positive MCC cell lines MS-1 and MKL-1 using cell proliferation assays where the IC 50 value for MS-1 was determined to be 85.7 nmol/L. 15 In addition, selinexor decreased the expression of DNA repair enzymes in MCC cells.…”