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Ordered biochemical program of gene expression in cancer cells
1Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, IN 46202-5119, USA. gweber1@iupui.edu
Biochemistry. Biokhimiia
|December 12, 2001
Summary
Cancer cells exhibit a unique gene expression reprogramming, causing metabolic imbalances. Targeting key enzymes like IMP dehydrogenase with drugs such as tiazofurin shows promise in leukemia treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Neoplasia involves complex alterations in cellular metabolism and gene expression.
- Understanding these changes is crucial for identifying cancer-specific vulnerabilities.
Purpose of the Study:
- To identify the ordered pattern of enzymic and metabolic imbalance in neoplasia.
- To elucidate the linkage between gene expression reprogramming and cancer transformation/progression.
- To identify potential targets for anticancer chemotherapy.
Main Methods:
- Utilized molecular correlation and key enzyme concepts with tumor models.
- Analyzed quantitative and qualitative gene expression alterations.
- Investigated metabolic pathways including pyrimidine, purine, and carbohydrate metabolism.
Main Results:
- Discovered an ordered pattern of enzymic and metabolic imbalance characteristic of neoplasia.
- Identified reprogramming of gene expression as the cause, involving reciprocal control of enzyme activities.
- Observed isozyme shifts in key regulatory enzymes.
- Demonstrated selective advantages conferred by gene expression reprogramming to cancer cells.
Conclusions:
- Gene expression reprogramming is essential for neoplasia and provides selective advantages.
- Altered enzymology and biochemistry of cancer cells offer sensitive targets for chemotherapy.
- Targeting IMP dehydrogenase in leukemia with tiazofurin yielded significant clinical responses (77%).