Multiple Sclerosis Treatment and Melanoma Development

Abstract

Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution.

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

“…Malignancies mainly involved cases of skin tumors, including malignant melanoma and basal cell carcinoma, and lymphoma as has been demonstrated in some studies ( Carbone et al, 2020 ; Lebrun-Frenay et al, 2020 ). The other types of tumors were unexpected.…”

“…Animal studies have shown reproductive toxicity, but clinical data from clinical trials, prospective pregnancy registry, post-marketing cases, and available literature do not suggest an effect of NTZ exposure on pregnancy outcomes (Rommer and Zettl, 2018). Malignancies mainly involved cases of skin tumors, including malignant melanoma and basal cell carcinoma, and lymphoma as has been demonstrated in some studies (Carbone et al, 2020;Lebrun-Frenay et al, 2020). The other types of tumors were unexpected.…”

Vesicle Fusion as a Target Process for the Action of Sphingosine and Its Derived Drugs

“…In relationship to neuronal function, effects limiting the proliferation of neuroblastoma [77], glioblastoma [78], and medulloblastoma cells [79] have been reported. Non-neuronal cancers such as, leukaemia [80], breast [81], melanoma [82], and others, seems also to benefit from such anti-proliferative effects. It is believed that the apoptosis is of mitochondrial origin, involving the dramatic reduction of mitochondrial membrane potential, the release of cytochrome c, and activation of caspases [85], and in consequence activation of the apoptotic cascade.…”

“…In conclusion, studies of the molecular effects of sphingolipids on membrane fusion and related processes increase our understanding of the physiological regulation of neurosecretion and provide a promise to conceive new therapeutic approaches against neurological syndromes [67][68][69][70][71][72][73][74][75][76]90], and cancer [77][78][79][80][81][82][83]91].…”

“…The anti-tumour effects of FTY-720 are observed in cancers from other, non-neuronal origins, for example in the treatment of leukaemia [80], with the effect being unrelated to sphingosine-1P receptors, but also in halting proliferation of breast cancer [81], melanoma [82], and myeloma cells [83], in a variety of mouse models.…”