Functional Genomics and the Development of Pathogenesis-Targeted Therapies for Kaposi‘s Sarcoma

Abstract

Kaposi's sarcoma (KS) is a multifocal angioproliferative disorder affecting the skin, mucosa and viscera of individuals infected with human herpesvirus-8 (HHV-8; also Kaposi's sarcoma-associated herpesvirus [KSHV]). KS is the most common neoplasm in AIDS patients; the clinical outcome of AIDS-KS is significantly improved by highly active antiretroviral therapy (HAART). However, in Africa, where the severest manifestations of KS occur, there is limited access to these and other effective but expensive drugs. Here we present a review of current efforts to identify novel therapeutic targets for the treatment of KS using functional genomics, with recommendations regarding the development of economically feasible treatments for use in Africa.

Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi’s sarcoma and P. falciparum malaria

“…Sixth, the probability of recrudescence of KS in patients treated with HAART later in life is unpredictable. There is, therefore, an urgent need for a multi-pronged therapeutic approach aimed at developing strategies that are appropriate to the prevailing epidemiologic state of the disease, with the overall goal being improvement of the treatment outcome for KS patients in sub-Saharan Africa and other resource-limited parts of the world (McAllister et al, 2005). …”

c-Kit (CD117) expression in classic Kaposi’s sarcoma

“…Preclinical studies have found that imatinib mesylate also induces regression of KS lesions. The data suggest that pharmacological agents that inhibit c‐Kit activity might be an important option for the treatment of KS, 17–25 but it is not yet clear whether the immunohistochemical detection of c‐Kit activity in KS lesions is a reliable indicator of a response to anti‐c‐Kit treatments.…”

Role of haem oxygenase-1 in microbial host defence

“…In contrast to the putative antiviral properties against HIV‐1, induction of HO‐1 may play a contributory role in Kaposi's sarcoma (KS), a multifocal angioproliferative disorder following infection with human herpesvirus‐8 (HH8, also known as Kaposi's sarcoma‐associated herpes virus, KSHV) (McAllister et al ., 2004). KS represents one of the most common AIDS‐associated malignancies.…”

“…KS represents one of the most common AIDS‐associated malignancies. An upregulation of both HO‐1 mRNA and protein were found in AIDS‐KS tissue, as well as in KSHV‐infected dermal microvascular endothelial cells (Cornelissen et al ., 2003; McAllister et al ., 2004). The fact that HO‐1 is upregulated is not an unexpected occurrence, as KS is characterized by angiogenesis, a physiological process that critically depends on HO‐1 (Dulak et al ., 2004; Dulak et al ., 2008).…”