Kaposi sarcoma

Abstract

Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; its appearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored.

PDGFRA Defines the Mesenchymal Stem Cell Kaposi’s Sarcoma Progenitors by Enabling KSHV Oncogenesis in an Angiogenic Environment

“…This is consequence of the need for specific host environmental factors or conditions such as immunosuppression, which are necessary to enable the expression of the oncogenic viral gene expression programs leading to full viral-mediated cellular transformation [1]. Kaposi’s sarcoma (KS) is an AIDS-defining cancer and a major global health challenge caused by the Kaposi’s sarcoma-associated herpesvirus (KSHV) [2–4]. It is characterized by the proliferation of spindle-shaped cells (SC), inflammatory infiltrate and abundant angiogenesis with blood vessel erythrocyte extravasation [2–5].…”

“…Endemic KS affects children, men, and women in Sub-Saharan Africa. Iatrogenic KS is characteristic of transplant immunosuppression, in particular, renal transplant, and epidemic or AIDS-associated KS predominantly affects MSMs infected with HIV [4]. AIDS-associated immunosuppression and HIV constitute important KS co-factors, yet other host factors may account for the oncogenicity of KSHV and HIV co-infection in specific “at-risk” populations [6], Although the incidence of AIDS-KS in the western world has declined since the implementation of ART, more than 50% of advanced AIDS-KS patients never achieve total remission [6–8], Moreover, KSHV prevalence and KS appear to be increasing in ART-treated HIV-infected patients with controlled viremias [9, 10].…”

RNA-sequencing analysis of a multistep and hit-and-run cell and animal model of KSHV tumorigenesis reveal the roles of mutations, CpG methylation, and viral-infection footprints in oncogenesis

“…Human viral oncogenesis is the consequence of the transforming activity of virally encoded oncogenes in combination with host oncogenic alterations (Mesri et al, 2014). Kaposi’s sarcoma (KS), caused by the Kaposi’s sarcoma-associated herpes virus (KSHV), is a major cancer associated with AIDS and is consequently a major global health challenge (Cesarman et al, 2019; Dittmer and Damania, 2016; Mesri et al, 2010). The KS tumors are characterized by intense angiogenesis and the proliferation of spindle cells that can affect the skin, mucosa and viscera, causing significant morbidity (Cesarman et al, 2019; Dittmer and Damania, 2016; Mesri et al, 2010).…”

“…Kaposi’s sarcoma (KS), caused by the Kaposi’s sarcoma-associated herpes virus (KSHV), is a major cancer associated with AIDS and is consequently a major global health challenge (Cesarman et al, 2019; Dittmer and Damania, 2016; Mesri et al, 2010). The KS tumors are characterized by intense angiogenesis and the proliferation of spindle cells that can affect the skin, mucosa and viscera, causing significant morbidity (Cesarman et al, 2019; Dittmer and Damania, 2016; Mesri et al, 2010). Although KS can be treated with anti-retroviral therapy and chemotherapy, it is estimated that more than a half of AIDS associated KS patients will not be cured (Cavallin et al, 2014; Cesarman et al, 2019).…”

“…The KS tumors are characterized by intense angiogenesis and the proliferation of spindle cells that can affect the skin, mucosa and viscera, causing significant morbidity (Cesarman et al, 2019; Dittmer and Damania, 2016; Mesri et al, 2010). Although KS can be treated with anti-retroviral therapy and chemotherapy, it is estimated that more than a half of AIDS associated KS patients will not be cured (Cavallin et al, 2014; Cesarman et al, 2019). Understanding the interplay between viral and cellular genes leading to KS carcinogenesis is paramount to developing rationally designed therapies for KS.…”