• Bertino, Joseph (PI)
  • Sawyer, Robert (PI)
  • Nord, L. (PI)
  • Mesa-Tejada, Ricardo (PI)
  • Stolfi, Robert (PI)
  • Martin, Daniel (PI)
  • Young, Charles (PI)

Project Details


The ultimate goal of the proposed research program is the development of
both safer and more effective combination therapy for cancer. Based on
principles of biochemical modulation, drug combinations, or drug-
metabolite combinations, selected on the basis of known or potential
biochemical interaction, will be utilized to manipulate relevant
biochemical pathways in a therapeutically beneficial manner to either
potentiate selective cytotoxicity in tumor cells, and/or to selectively
diminish toxicity in normal host cells. the control of serious host
toxicity is viewed as essential to the achievement of chemotherapeutic
cure, because the resulting operational increase in drug selectivity will
allow both a quantitative and a qualitative intensification of
chemotherapy. In addition to the specific "rescue" approach for
antimetabolite toxicity with the corresponding normal metabolite,
attempts will be made to prevent drug-induced toxicity by stimulating
more rapid hematopoietic recovery between drug treatment courses with
hematopoietic growth factors; also, selected agents with potential for
sparing, or for stimulating more rapid recovery in drug-damaged
intestinal epithelium will be evaluated. the goal is to increase both
the power and selectivity of the therapeutic attack, hopefully to the
level of cure of advanced, spontaneous solid cancer, first in a murine
model and then ultimately in patients. This approach requires the
integration of 3 projects: Project 1, Experimental Therapy; Project 2,
Biochemical Studies; Project 3, Clinical Studies. Preclinical therapy
studies (Project 1) will be performed entirely in vivo murine tumor
models. Therapeutic results from a particular drug manipulation,
obtained as expected on the basis of the basis of the biochemical
information that prompted that manipulation, will be confirmed on a
biochemical level (Project 2) to insure that the chemotherapeutic results
are related to the predicted biochemical changes. Biochemical analysis
of human tumors, before and after treatment, determine (and establish)
that the employed clinical dose is reproducing the same biochemical
changes that were responsible for the successful preclinical results.
Thus, the preclinical combined in vivo biological and biochemical
findings, Projects 1 and 2, lead to guidelines for Project 3's very
specific clinical trials.
Effective start/end date4/1/806/30/97


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)

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