Targeting the tumor vasculature strategies for combination therapy

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Abstract

The tumor vasculature is a well-recognized and increasingly popular target for the therapy of solid tumors, since it is reasonable to presume that damaging tumor vessels would affect the many tumor cells that depend on them for survival. Phenotypic and functional characteristics distinguish tumor vessels from the mature vasculature in normal tissues, thus providing selective targets for therapy of antineoplastic agents designed to prevent the formation of new vessels (anti-angiogenic therapy) or to damage the already formed vessels (vascular targeting/disrupting therapy). A number of approaches have been developed and have shown their efficacy in preclinical models, and more recently, in clinical studies. Combination therapies, including one or more angiogenesis inhibitors together with conventional means, constitute the new avenue to the treatment of progressive cancer disease. The choice of the combination/s, doses and schedules, as well as the sensitivity of the tumor, are some of the issues that need to be considered in the design of trials implementing this approach. No less important are the metabolic and pharmacokinetic interactions and unexpected toxicities that play a relevant role in treatment outcome. Here we highlight the critical factors that determine the success or failure of these treatments. Also analyzed is the relevance of the mechanism of action and the intrinsic activity of the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Special attention is given to the need to optimize scheduling and sequencing, through the use of reliable end points, in order to avoid adverse pharmacological interactions and to improve the antineoplastic efficacy of combination treatments.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalMedicina
Volume67
Issue numberSUPPL. 2
Publication statusPublished - 2007

Keywords

  • Angiogenesis inhibitors
  • Chemotherapy
  • Combination therapies
  • Tumor stroma
  • Vascular disrupting agents

ASJC Scopus subject areas

  • Medicine(all)

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