Cyclophosphamide and cancer: Golden anniversary

Research output: Contribution to journalArticle

Abstract

Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)638-647
Number of pages10
JournalNature Reviews Clinical Oncology
Volume6
Issue number11
DOIs
StatePublished - 2009

Fingerprint

Anniversaries and Special Events
Cyclophosphamide
Aldehyde Dehydrogenase
Neoplasms
Immunosuppressive Agents
Transplantation
Bone Marrow
Clinical Pharmacology
Poisons
Antineoplastic Agents
Autoimmune Diseases
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology

Cite this

Cyclophosphamide and cancer : Golden anniversary. / Emadi, Ashkan; Jones, Richard J; Brodsky, Robert A.

In: Nature Reviews Clinical Oncology, Vol. 6, No. 11, 2009, p. 638-647.

Research output: Contribution to journalArticle

@article{9965bd45c7c843f59d1331c07bec4a49,
title = "Cyclophosphamide and cancer: Golden anniversary",
abstract = "Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.",
author = "Ashkan Emadi and Jones, {Richard J} and Brodsky, {Robert A}",
year = "2009",
doi = "10.1038/nrclinonc.2009.146",
language = "English (US)",
volume = "6",
pages = "638--647",
journal = "Nature Clinical Practice Oncology",
issn = "1759-4774",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Cyclophosphamide and cancer

T2 - Golden anniversary

AU - Emadi, Ashkan

AU - Jones, Richard J

AU - Brodsky, Robert A

PY - 2009

Y1 - 2009

N2 - Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.

AB - Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.

UR - http://www.scopus.com/inward/record.url?scp=70350786392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350786392&partnerID=8YFLogxK

U2 - 10.1038/nrclinonc.2009.146

DO - 10.1038/nrclinonc.2009.146

M3 - Article

C2 - 19786984

AN - SCOPUS:70350786392

VL - 6

SP - 638

EP - 647

JO - Nature Clinical Practice Oncology

JF - Nature Clinical Practice Oncology

SN - 1759-4774

IS - 11

ER -