Redefining the target: Chemotherapeutics as antiangiogenics

K. D. Miller, C. J. Sweeney, Jr Sledge

Research output: Contribution to journalReview article

371 Scopus citations


Angiogenesis, or new blood vessel formation, is now known to play an important role in both growth and metastasis of many cancers. The central importance of angiogenesis and the understanding of how new blood vessels are formed, has led to novel therapies designed to interrupt this process. Though specific antiangiogenic compounds have only recently entered the clinic, they herald a new era, one in which biology is the basis for therapy. The intense interest in angiogenesis has also lead to a re-examination of the activity of many established cytotoxic agents. Claims of antiangiogenic activity abound, unfortunately, with no common criteria and often tittle evidence of clinical relevance. What are we to think? Have oncologists unknowingly been administering antiangiogenic therapy all these years? If chemotherapeutics are really antiangiogenics in disguise, why have they failed to cure most solid tumors? Might the hard-learned lessons of chemotherapy resistance pertain to the novel antiangiogenics as well? Though we can offer no certain answers to these important questions, we do offer a framework on which to order the rapidly burgeoning literature. We suggest criteria by which a cytotoxic agent might reasonably be considered to have meaningful antiongiogenic activity. Finally, we describe potential mechanisms of resistance to antiangiogenic chemotherapies-some of which may apply to the pure antiangiogenics currently in development.

Original languageEnglish (US)
Pages (from-to)1195-1206
Number of pages12
JournalJournal of Clinical Oncology
Issue number4
StatePublished - Feb 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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