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Breast Cancer Resistance to Cyclophosphamide and Other Oxazaphosphorines.

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Annual rept. 1 Oct 96-30 Sep 97

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Cyclophosphamide is widely used to kill breast cancer cells that detach from primary tumors prior to the surgical removal of the latter and that relocate in various parts of the body where they usually cannot be detected and where they multiply. Unfortunately, even though cyclophosphamide is amongst the best available drugs for this purpose, its use rarely results in cures because, amongst these relocated cancer cells, there are, or soon are, some that can defend themselves against cytoxan and therefore are not killed by it. The objective of our studies is to find out how such cells do this and, then, to develop strategies that would eliminate, negate or circumvent the defensive measures used by them to survive. Thus far, our investigations suggest support the following 1 prognostic determinants that can be used to identify patients for whom cyclophosphamide therapy would prove to be futile include cellular levels of ALDH-1 and, perhaps, ALDH-3, 2 clinical ALDH-3 mediated breast cancer cell resistance to cyclophosphamide may be overcome by the co-administration of gossypol or other drugs that inhibit ALDH-3, and 3 consistent with existing information, but yet to be unequivocally established, it may be prudent to avoid certain dietary constituents when taking Cyclophosphamide because they may decrease the sensitivity of breast cancer cells to it by inducing ALDH-3 in these cells.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Pharmacology

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