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 language | English (US) |
|---|---|
| Pages (from-to) | 102-109 |
| Number of pages | 8 |
| Journal | Seminars in Oncology |
| Volume | 29 |
| Issue number | 1 SUPPL. 4 |
| State | Published - 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Tirapazamine
T2 - Prototype for a novel class of therapeutic agents targeting tumor hypoxia
AU - Gandara, David R
AU - Lara, Primo N
AU - Goldberg, Zelanna
AU - Le, Quynh T.
AU - Mack, Philip
AU - Lau, Derick H
AU - Gumerlock, Paul H.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11894020
AN - SCOPUS:0036121220
VL - 29
SP - 102
EP - 109
JO - Seminars in Oncology
JF - Seminars in Oncology
SN - 0093-7754
IS - 1 SUPPL. 4
ER -