Protection of Normal Cells Against Toxic Effects of Chemotherapy by Reversible G1 Arrest
Abstract
Treatment of cancer with chemotherapy and radiation therapy has severe side effects that damage healthy proliferating cells such as hematopoietic precursors, hair follicle, cells and the epithelial lining of the intestine. These side effects often limit the doses of chemotherapy administered, allowing tumor cells to gain growth advantage by escaping treatment and developing drug resistance. Since cancer therapy targets proliferating cells and tissues, all cells that proliferate, whether normal or tumor are affected by the treatment. If however the normal dividing cells in the body were to stop proliferating reversibly, the toxic effects of chemotherapy would potentially be diminished. Here, we introduce a novel therapeutic strategy to selectively target cancer cells, while leaving normal proliferating cells intact by taking advantage of differences in cell cycle regulation between normal and tumor cells. The approach taken for this "protection" strategy involves two steps: First, the normal proliferating cells are blocked in the G0/G1 phase of the cell cycle by pre-treatment with cytostatic, non-lethal agents. Tumor cells will not respond to these agents, because they have lost the GO/1 checkpoint; they will continue to proliferate. Next, both normal and tumor cells are treated with conventional chemotherapeutic agents which will specifically kill proliferating tumor cells. Normal cells are protected because of the G0/G1 mediated reversible arrest achieved in the first step. Our goal for this one year concept award is to examine the feasibility of our hypothesis against drug resistant tumor cells in culture and to initiate a pilot study in vivo to examine the pre-clinical applicability of our hypothesis in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA410238
Entities
People
- Khandan Keyomarsi
Organizations
- The University of Texas MD Anderson Cancer Center