Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization of cancer chemotherapeutic regimens

Cancer Chemotherapy and Pharmacology
L Sreerama, N E Sládek

Abstract

Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular content of two aldehyde dehydrogenases, viz ALDH1A1 and ALDH3A1, and glutathione. Breast tumor levels of these "determinants of cellular sensitivity to the oxazaphosphorines" are known to vary widely, and the decision as to whether or not to use an oxazaphosphorine as part of the therapeutic strategy to treat breast cancer in any given patient is likely to depend, in large part, on the levels of these determinants in that cancer. ALDH1A1, ALDH3A1, and glutathione levels can be easily quantified in primary breast tumors and in detectable metastatic breast tumors present in axillary lymph nodes because the amounts of tissue required for the desired analysis can be readily obtained, whereas these levels cannot be quantified in residual metastatic breast cancer cell populations, i.e., those that escape detection and/or that are inaccessible to surgical harvest. The inability to directly quantify residual metastatic breast cancer c...Continue Reading

Citations

Aug 21, 2012·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Michael P GamcsikO Michael Colvin
Mar 5, 2003·Journal of Biochemical and Molecular Toxicology·Norman E Sládek
Dec 31, 2011·Free Radical Biology & Medicine·G MuzioR A Canuto
Feb 26, 2011·Chemico-biological Interactions·Bibek ParajuliThomas D Hurley
Feb 22, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jing XuZhuo Georgia Chen
Dec 31, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M Michael, M M Doherty
Apr 30, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Serkan SertelThomas Efferth
Dec 1, 2005·Current Protocols in Toxicology·Lakshmaiah Sreerama, Norman E Sládek

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