EDITORIAL

ELECTRONIC JOURNAL OF BIOTECHNOLOGY

....MOVING FROM SCIENCE TO DEVELOPMENT...


The need to strength collaborative teams in lung cancer research


It is estimated that at least 75% of the cancers are caused by chemical compounds, according to WHO approximately 10 million people are diagnosed with cancer annually and more than 6 million die of the disease every year. In the period 1990-2000 an increase of around 19% in incidence and 18% in mortality has been observed. It is expected by 2020 that the number of cancer cases will double to 20 millions with an annual death of 12 millions. Lung cancer is the major cause of death from cancer, accounts for 1.1 million deaths a year and 17.8% of all cancer deaths, and is the type of cancer with worse prognosis since no effective treatment is available; the five year survival rate for lung cancer patients is less than 15%.

Tobacco smoking is the main known cause of lung cancer related death worldwide. The incidence of the disease is generally related to environmental, life style, diet and host factors. Main environmental factors include air, water and soil air pollution, as well as occupational exposures. The main host factor are: genetic pattern, carcinogen exposure, carcinogen metabolism, DNA repair activity, oncogene and tumour suppressor expression and nutritional status.

Molecular biology and genetic engineering advanced laboratory methods used in combination with analytical epidemiology and bioinformatic tools help to understand the mechanisms of chemical carcinogenesis and to identify at the molecular level, specific exogenous or/and host factors that play a role in human cancer causation. Molecular epidemiology of lung cancer has focused on environmental causes because is believed that one of the main factor of incidence is exogenous and hence preventable. Biomarkers of internal dose, of biologically effective dose, of response and susceptibility give important information for prevention and treatment of the disease. Molecular endpoints used in studies of molecular carcinogenesis which give key information about both genetic and environmental susceptibility factors: include metabolites in body fluids, DNA and protein adducts, mutations in reporter genes, in oncogenes and in suppressor genes, genomic instability, aberrant gene expression and altered cell culture.

Polymorphisms in genes coding for enzymes involved in the metabolism and detoxification of carcinogens including many cytochromes P-450 that codify for Phase I enzymes or genes that codify for conjugation Phase II enzymes, or for DNA repair enzymes and for tumour suppressor proteins might be determinant in the risk to lung cancer by environmental exposure. The frequency of many of these polymorphisms is related to lung cancer susceptibility and might varies within different etnias suggesting that some populations around the world might be more susceptible to environmental carcinogens pollutants.

It is hoped that a more unified approach to cancer epidemiology and genetics will identify those combinations of genetic susceptibility and environmental exposures that lead to significant increases in risk at the individual and population level. This could lead to changes in lifestyle and avoidance of specific exposures in genetically susceptible individuals.

The complete sequencing of the human genome is allowing the identification of expressed sequences and polymorphic sequences providing information that is increasingly available to medical researchers that make possible to visualize in the near future more personalized protocols for the disease treatment as well as to identify persons with higher risk. Thus, the discovery of genes involved in the pathogenesis may lead to new targets for diagnosis and treatment. A knowledge in the polymorphisms that make each of us unique individuals could be the key in the future for predicting individual risks for developing the disease as well as the individual responses to antineoplasic drugs. The cancer researchers are presently searching in genome databases trying to identify candidates for genes important in lung cancer pathogenesis. Chromosomal aberrations and loci of chromosomal deletions have already been defined in lung cancer and with the increasing availability of gene maps we are now seeing an acceleration in our recognition of new genes involved in lung cancer pathogenesis.

Some of the most promising applications of genomics to lung cancer research come from measurements of the gene expression of cancer cells. Thus, serial analysis of gene expression, oligonucleotide arrays and cDNA arrays are now tools that allow investigators to measure the expression of thousands of gene in a single experiment. This help to learn about selected clones, genes over expressed in certain types of lung cancers and to identify potential therapeutic targets. Gene arrays have offered the opportunity to test large numbers of gene as potential predictive markers of clinical applications.

New genomic techniques will facilitate changes in tumour classification and consequently will be more useful for therapy. Although gene expression patterns are closed linked to cell’s function, it is ultimately genetic alterations that are responsible for the cancer phenotype. Thus, for detecting mutations, genomic DNAs techniques such as oligonucleotide arrays can represent a series of different sequences for each gene, including wild type and single-base mistmatched sequences.

Promising new proteomics techniques might not only measure protein levels related to the disease but might also recognize post translational modifications of proteins. Integrating these measurements with those of gene expression could add a whole new dimension to our understanding of lung cancer. Due to poor survival rates, the development of novel techniques for early diagnosis, prevention and therapies is a high priority to diminish lung cancer incidence, and mortality. Thus, clinical scientists, pathologists, molecular biologists, statisticians and informatic specialists working as a team will make lung cancer genomics and proteomic programs successful. Collaborative efforts will be increasingly important in cancer research because sophisticated tools requires specialized expertise.


Marta Adonis and Lionel Gil
Programa de Biología Molecular y Celular
Facultad de Medicina
Universidad de Chile
Santiago, Chile
Tel: 56 2 6786068
Fax: 56 2 7376320

lgil@machi.med.uchile.cl
http://icbm.cl/