الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 108 |  |  |
| | | from | 108 | | |
Abstract
The initiation and progression of human neoplasia is a multistep process invol,:,ing the accumulation of genetic changes in somatic cells. These genetic changes consist of the activation of oncogenes and the inactivation or loss of tumor suppressor genes.
Oncogenes are altered version of normal celluler genes called proto-oncogenes. Proto-oncogenes are a diverse group of genes involved in the regulation of cell growth. The function of protooncogenes include growth factors~ and regulatores of programmed cell death. Proto-oncogenes may be activated by mutation, chromosomal rearrangement, or genes amplification.
The discovery of oncogenes represented a breakthrough for our understanding of the molecular & genetic basis of cancer. Oncogenes have also provided important knowledge concerning the regulation of normal cell proliferation, differentiation, and programmed cell death. The identification of oncogene abnormalities has provided tools for the molecular diagnosis and monitoring of cancer. Most important, oncogenes represent potential targets for new types of cancer therapies. It is hoped that a new generation chemotheropeutic agents directed at specific oncogene targets will be developed. The goal of these new drugs will be killing to cancer cells selectively while sparing normal cells.
Tumor suppressor genes, which also participate in the regulation of normal cell growth, are usually inactivated by point mutations coupled with the loss of the normal allale. Much evidence has now been obtained to demonstrate that inactivating mutation in tumor suppressor and DNA
repair genes are critical in the development of many types of human tumors. Additional evidence for the existence of tumor suppressor genes and their important in. tumorigenesis emerged gradually from studies of chromosome losses in tumor cells using cytogenetic and molecular genetic techniques. In the past decade, nearly a dozen of tumor suppressor genes have been isolated by molecular cloning techniques. In some cases these genes are lost or inactivated in germ-line, more often they are inactivated by somatic mutations arising tumor development.
The tumor suppressor genes are likely to function in a wide variety of growth regulatory pathways. The products of some tumor suppressor genes may act directly to oppose the function of oncogenes, whereas others may’ interact indirectly with oncogenes in pathways of growth and differentiation.
In addition, the means by which loss of function mutations in the DNA repair pathway genes promotes the development of specific cancer types is not fully understood. A more complete description of tumorigenesis will undoubtedly emerge with the identification of additional tumor suppressor and DNA repair pathway genes, the detailed characterization of their normal cellular fanctions, and the elucidation of mutations that inactivate these genes in human tumors. These findings not only will provide new insights into cancer pathogenesis but also will be of great importance in improving the management and treatment of patients with cancer.