Classic Kaposi's sarcoma treated with topical rapamycin

Abstract

Kaposi's sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus 8 (HHV-8). Current research efforts have focused on the study of the relative role of KSHV-encoded genes in Kaposi's sarcomagenesis in order to identify novel mechanism-based therapies for patients suffering from this tumor. Although several viral genes have potential for KS pathogenesis, compelling data point to the KSHV-encoded G protein-coupled receptor (vGPCR) as a leading candidate viral gene for the initiation of KS. Interestingly, the oncogenic potential of vGPCR seems to correlate with its capacity to activate the mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin, the prototypical inhibitor of the mTOR signaling pathway, has recently emerged as an effective treatment for KS when administered orally. In this case report, we present an immunocompetent patient with KS lesions treated with topical rapamycin achieving clinical and histologic healing after 16 weeks of treatment. The topical application of rapamycin could be a novel therapeutic option for the treatment of KS.

Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin

“…Clinically, psoriasis and classic Kaposi’s sarcoma have been successfully treated with topical rapamycin [23, 24]. In mouse models, topical pretreatment with rapamycin suppressed acute UVB-induced skin thickening by inhibiting epidermal proliferation [14].…”

Topical rapamycin (sirolimus) for the treatment of uncomplicated tufted angiomas in two children and review of the literature

“…This inhibits lymphatic vessel regeneration and invasion and is the proposed mechanism for the effectiveness of topical rapamycin in microcystic lymphatic malformations . It is purported that inhibition of angiogenesis and low VEGF secretion is responsible for efficacy against Kaposi sarcoma . Given the known upregulation of VEGF isoforms in TA and the lymphatic‐vascular histologic phenotype of TA, we hypothesize that topical rapamycin is acting through the inhibition of vascular and lymphatic endothelial cells in TA …”

“…In previous studies, blood levels of topical rapamycin have been lower than the individual laboratory detection limits . Given this, we elected not to measure rapamycin levels in our cases and monitored the patients clinically for any side effects.…”

“…24 In previous studies, blood levels of topical rapamycin have been lower than the individual laboratory detection limits. 14,15,19,20,22,27,28 Given this, we elected not to measure rapamycin levels in our cases and monitored the patients clinically for any side effects. Topical rapamycin has been reported for use in children as young as 2 years of age, and oral rapamycin has been used in children with vascular anomalies from 21 days of age.…”

Classic Kaposi's sarcoma treated with topical 0.5% timolol gel

“…Topical treatment would be ideal for patients with limited disease confined to the skin, since it may satisfactorily slow progression of classic KS for several years with lower risks of systemic side effects. In this way, some topical agents have been used with various results, including 5% imiquimod cream , 0.5% rapamycin ointment , 0.1% alitretinoin gel and very recently, 0.5% timolol maleate solution . We report here two cases of classic KS successfully treated with topical timolol.…”