Tirapazamine: Prototype for a novel class of therapeutic agents targeting tumor hypoxia

David R Gandara, Primo N Lara, Zelanna Goldberg, Quynh T. Le, Philip Mack, Derick H Lau, Paul H. Gumerlock

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Preclinical models in vitro and in vivo have shown that tumor hypoxia alters the malignant cell phenotype, selecting for p53 mutations, stimulating angiogenesis and metastasis, and markedly reducing the efficacy of both radiotherapy and chemotherapy. Similarly, clinical studies measuring pretreatment tumor oxygen status confirm that the presence of hypoxia confers a negative impact on local control, disease-free survival, and overall survival. Despite these data and extensive past research efforts, the promise of developing selective hypoxic-cell sensitizers has been largely unfulfilled. In contrast, tirapazamine is the rationally designed prototype for a new class of therapeutic agents targeting tumor hypoxia: hypoxic cytotoxins. Tirapazamine is bioreductively activated in hypoxic cells and has been shown to potentiate the cytotoxicity of radiation and a number of chemotherapeutic drug classes, in particular platinum compounds and taxanes. This article reviews the preclinical and clinical development of tirapazamine, as well as current trials in non-small cell lung cancer designed to provide proof of principle for this new category of cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalSeminars in Oncology
Volume29
Issue number1 SUPPL. 4
StatePublished - 2002

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tirapazamine
Platinum Compounds
Taxoids
Cytotoxins
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Neoplasms
Radiotherapy
Therapeutics
Radiation
Oxygen
Neoplasm Metastasis
Phenotype
Drug Therapy
Mutation
Research
Pharmaceutical Preparations
Tumor Hypoxia

ASJC Scopus subject areas

  • Oncology

Cite this

Tirapazamine : Prototype for a novel class of therapeutic agents targeting tumor hypoxia. / Gandara, David R; Lara, Primo N; Goldberg, Zelanna; Le, Quynh T.; Mack, Philip; Lau, Derick H; Gumerlock, Paul H.

In: Seminars in Oncology, Vol. 29, No. 1 SUPPL. 4, 2002, p. 102-109.

Research output: Contribution to journalArticle

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