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An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
Published on: August 25, 2017
Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma
Marc-Antoine Valantin1, Léna Royston2,3, Maxime Hentzien4
1Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health Institute (iPLESP), INSERM U1136, Sorbonne University, 75013 Paris, France.
Abstract:
In patients with Kaposi's sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.
Insights
New therapies like anti-angiogenic drugs and immune checkpoint inhibitors show promise for refractory Kaposi
Area of Science:
- Oncology
- Immunology
- Vascular Biology
Background:
- Kaposi's sarcoma (KS) management requires durable remission of skin and visceral lesions.
- Standard chemotherapy is effective, but refractory cases necessitate alternative treatments.
- Angiogenesis and HHV-8 immunity are key factors in KS pathogenesis.
Purpose of the Study:
- To review potential therapeutic options for recurrent or refractory Kaposi's sarcoma.
- To discuss the role of anti-angiogenic and immune checkpoint blockade therapies.
- To highlight the need for clinical trials evaluating novel agents.
Main Methods:
- Literature review of systemic chemotherapies, anti-angiogenic drugs, and immune checkpoint inhibitors.
- Discussion of anti-herpesvirus agents.
- Analysis of therapeutic targets in KS pathogenesis.
Main Results:
- Pomalidomide, an anti-angiogenic agent inhibiting VEGF, is a promising treatment and FDA-approved.
- Immune checkpoint blockade may restore immunity against HHV-8, improving tumor control.
- Limited case series show success, but no marketing approval exists for checkpoint inhibitors in KS.
Conclusions:
- Targeted agents and immunomodulators offer potential for refractory KS.
- Further clinical trials are essential to determine efficacy and safety.
- Monitoring adverse effects is crucial for these novel therapies.
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