The lung cancer mystery

We dwell a lot on the many unknowns about the bird flu H5N1 virus. What could make it easily transmissible between people? What determines what host it infects? What makes it so virulent? With the threat of a pandemic looming it can sometimes seem the virus is an especially, maybe even uniquely, wily foe. Every move we make it changes to outsmart us. We remain helpless. But the same is true of so many other deadly threats, including one that killed over 160,000 people in the US last year: lung cancer. What makes lung cancer so deadly? Why are some lung cancers so aggressive? What makes it spread? Are all lung cancers deadly or only some of them? As with H5N1, we are looking in the genetics of the lung cancer cell and a new study, just published in Nature, looks at what genes are consistently different in lung cancer by analyzing hundreds of tumors:

Of particular interest was a specific proto-oncogene called NKX2-1 that appears involved in as many as 12 percent of lung adenocarcinomas -- the most common cause of cancer deaths worldwide, said the group, whose work was in part financed by the National Human Genome Research Institute (NHGRI). The group noted, however, that analysis indicates that many of the genes that play a role in the disease remain to be discovered.

[snip]

The team found 57 frequent genomic changes in their analysis of the genetics of tumors taken from lung cancer patients. Of these, 15 are linked to genes known to be involved in lung cancer. The rest remain to be discovered.

The gene NKX2-1 is essential in the development of cells that line the alveoli of the lungs. Mice lacking the gene die at birth because they cannot breathe. However, it is a proto-oncogene, which means that it can mutate into a gene that promotes development of cancer.

Lung adenocarcinoma is the leading cause of cancer death worldwide. Using gene chip or microarrays, researchers compared the genomes of 371 lung adenocarcinomas to 242 normal lung samples using special gene chips to analyze approximately 250,000 genetic markers. Their analyses identified areas of genetic material that has been repeated or deleted in the tumors. Among these were six areas currently associated with known mutations in lung cancers.

The most common event was an increase in genetic information on one arm of chromosome 14, where NKX2-1 is found in that area of the chromosome. Using a variety of techniques, including RNA interference, they determined that NKX2-1 is essential for the survival of lung cancer cell lines that express the gene. (Medical News Today)

Cancer is not a simple disease. Cancer cells are normal cells that have been reprogrammed to behave aberrantly: they divide when they shouldn't and they comfortably grow in places where they shouldn't. They don't care about the welfare of the tissues around them or the body in which they out compete normal cells. They are deviant cells.

160,000 people die a year from lung cancer. Every year. Year after year. We know cigarettes killed most of them but we don't know exactly how any more than we know what would make H5N1 easily transmissible between people.

Mysteries -- deadly mysteries -- abound.