The molecular and cellular basis of human lung cancer

A. F. Gazdar

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. How can so many changes develop in one cell? One possible explanation is the 'field cancerization' theory, that states that all or much of the aerodigestive tract epithelium has been mutagenized, perhaps as the result of exposure to tobacco products or other carcinogens. The molecular changes include activation of dominant oncogenes (myc family, K-ras and HER/2neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and rb as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Many of the well characterized molecular changes may function as negative prognostic factors for survival in subsets of lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However because of the difficulties in serially sampling the respiratory tract, only a modest amount of data has been collected to date. It appears that deletions of chromosome 3p, hyperproliferation and aneuploidy are early changes while p53 mutations appear later in the preneoplastic cascade. Documentation of intermediate markers for lung cancer and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.

Original languageEnglish (US)
Pages (from-to)261-267
Number of pages7
JournalAnticancer Research
Volume14
Issue number1 B
StatePublished - 1994

Fingerprint

Lung Neoplasms
Epithelium
Genes
Neoplasms
myc Genes
Chromosomes, Human, Pair 3
Growth Factor Receptors
Carcinoma in Situ
Small Cell Lung Carcinoma
Chemoprevention
Metaplasia
Aneuploidy
Regulator Genes
Tumor Suppressor Genes
Drug Resistance
Cytogenetics
Tobacco Products
Documentation
Respiratory System
Carcinogens

Keywords

  • Human, molecular and cellular basis
  • Lung cancer
  • Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The molecular and cellular basis of human lung cancer. / Gazdar, A. F.

In: Anticancer Research, Vol. 14, No. 1 B, 1994, p. 261-267.

Research output: Contribution to journalArticle

Gazdar, AF 1994, 'The molecular and cellular basis of human lung cancer', Anticancer Research, vol. 14, no. 1 B, pp. 261-267.
Gazdar, A. F. / The molecular and cellular basis of human lung cancer. In: Anticancer Research. 1994 ; Vol. 14, No. 1 B. pp. 261-267.
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