NEO412: A temozolomide analog with transdermal activity in melanoma in vitro and in vivo.

NEO412: A temozolomide analog with transdermal activity in melanoma in vitro and in vivo. Oncotarget. 2018 Dec 11;9(97):37026-37041 Authors: Swenson S, Silva-Hirschberg C, Wang W, Singh A, Hofman FM, Chen KL, Schönthal AH, Chen TC Abstract Despite new treatments introduced over the past several years, metastatic melanoma remains difficult to cure. Although melanoma in situ (MIS) has better prognosis, it relies heavily on thorough surgical excision, where ill-defined margins can pose a challenge to successful removal, potentially leading to invasive melanoma. As well, MIS in the head and neck area can create serious aesthetic concerns with regard to the surgical defect and substantial scar formation. Toward improved treatment of localized melanoma, including the targeting of unrecognized invasive components, we have been studying a novel agent, NEO412, designed for transdermal application. NEO412 is a tripartite agent that was created by covalent conjugation of three bioactive agents: temozolomide (TMZ, an alkylating agent), perillyl alcohol (POH, a naturally occurring monoterpene with anticancer properties), and linoleic acid (LA, an omega-6 essential fatty acid). We investigated the anti-melanoma potency of NEO412 in vitro and in mouse models in vivo. The in vitro results showed that NEO412 effectively killed melanoma cells, including TMZ-resistant and BRAF mutant ones, through DNA alkylation and subsequent apoptosis. in vivo, NEO4...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research