The cell cycle: Probing new molecular determinants of resistance and sensitivity to cytotoxic agents
Deisseroth, A.B.; DeVita, V.T.
Cancer Journal from Scientific American 1(1): 15-21
1995
ISSN/ISBN: 1081-4442 PMID: 9166447 Document Number: 451917
The introduction of chemotherapy in the fifth and sixth decades of this century has resulted in the development of curative therapeutic interventions for patients with several types of solid tumors and hematopoietic neoplasms. The important obstacles encountered in the use of chemotherapy have been toxicity on the normal tissues of the body and the presence of mutations that confer resistance to these chemotherapeutic agents. During the past 5 years, the application of molecular analysis to the DNA of normal and neoplastic cells has uncovered some of the mechanisms through which chemotherapy induces cell death, and the changes within these cells that can confer either sensitivity or resistance to these cells. This new level of understanding of the mechanisms through which chemotherapy works, and by which genetic change can result in resistance to this therapy, has opened the door to totally new paradigms of treatment. These paradigms use molecular, genetic, and biologic therapies together to increase the sensitivity of abnormal cells to treatment, and to protect the normal tissues of the body from therapy-induced side effects. The implementation of these new strategies, which is already well under way, promises to dramatically change the way in which therapy is delivered over the next few years, and to improve the outcome especially in patients with neoplasms that currently are resistant to conventional dose therapy.