title: Therapy of AIDS-associated Kaposi's sarcoma: targeting pathogenetic mechanisms.
abstract: Only a small number of the many agents with the potential to inhibit factors known to stimulate KS growth have been tested clinically, and many were investigated at a time when treatment options for HIV infection were relatively ineffective. The failure of some of these agents to induce KS regression may not signify failure to achieve a relevant biologic effect in all cases, but may simply mean that in a neoplasm that expresses a broad array of growth factors, inhibition of a single factor may be insufficient to achieve tumor regression. Moreover, agents that inhibit angiogenesis may be expected to stabilize tumors rather then eradicate them, but tumor stabilization is a difficult endpoint to quantify. In fact, given the redundancy of growth factors believed to be involved in KS development, it is perhaps remarkable that members of several classes of agents (eg, a synthetic retinoid, an MMPI, thalidomide, IL-12) have induced KS regression in a substantial minority of patients. It is likely, however, that drug combinations that target several pathogenetic mechanisms will be more effective than will single drugs in suppressing KS growth. A particular need. especially in the early evaluation of therapies aimed at specific pathogenic targets, is the development of assays to measure specific biologic effects (eg, changes in the activity of signal transduction pathways within tumor biopsy specimens) related to the agent's putative mechanism of action. Greater availability and clinical application of these types of markers of biologic efficacy may speed the identification of potentially active agents that could then be "fast tracked" into larger efficacy trials and combination studies.
authors.affiliation: Clinical Immunology Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. krowns@mskcc.org
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000209:etiology / Q000628:therapy* / Q000821:virology; D020533:Angiogenesis Inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D015497:HIV-1; D019288:Herpesvirus 8, Human; D006801:Humans; D007167:Immunotherapy; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000628:therapy* / Q000821:virology
chemical_list: D020533:Angiogenesis Inhibitors; D016207:Cytokines