The role of chromosome 3 deletions in lung cancer

Abstract

Lung cancer is currently the major cause of cancer death in the United States in both males and females, accounting for approximately 142,000 deaths per year in the United States [14]. This disease remains both highly and rapidly fatal. Despite the advances enjoyed in many other areas of medicine, the response to current therapy of lung cancer remains unchanged over the past 20 years. One exception to this is the small cell variety of lung cancer, for which advances in chemotherapy and radiation therapy have made major improvements in the response rates. Despite these advances, the survival rate for small cell lung cancer is less than that of other forms of lung cancer [4]. Improvements in the treatment of lung cancer can only be expected if new therapeutic modalities or strategies are developed. Such advances in treatment must be based on advances in the knowledge of the biology of the disease. Recent information regarding small cell lung cancer on a cellular and molecular level demonstrates the prognostic and therapeutic capabilities of such approaches. Improvements in treatment can be expected only if these molecular and cellular mechanisms are understood and their significance appreciated. Recent molecular genetic work has shown that lung cancer, both small cell and non-small cell, is associated with loss of genetic material from chromosomes 3, 11, 13 and 17 [16, 191. With the loss of heterozygosity at a genetic locus, several mechanisms can be hypothesized to account for an association with a malignancy. A recessive gene, such as an oncogene or a mutant gene, could be unmasked or, alternatively, the loss of a dominant gene or anti-oncogene, could result in activation of a malignant process. A regulatory gene, such as the c-erb-A gene which will be discussed, may play a role in repressing the transcription of other genes which cause cancer; the loss of such a regulatory gene could permit other genes to cause cancer. This