Curing Lung Cancer
One of the great tragedies of this century has been the widespread addiction of large numbers of people to tobacco. An enormously profitable commercial enterprise, the production and marketing of cigarettes now affects a significant fraction of all the people on the planet. Many cigarette smokers are now dying of lung cancer, so it is with real excitement that researchers are now pursuing investigations that offer real hope of curing this deadly disease. For decades it has been clear that cigarette smoking is both habit-forming and somehow linked to lung cancer, but the exact way in which tobacco and lung cancer are linked has evaded researchers. In the last year, however, scientists have uncovered the link. It turns out that tobacco smoke contains a chemical called benzo (a) pyrene which disrupts a key element in the bodys normal defense against cancer. In studying how this tobacco chemical produces cancer, researchers have stumbled across an opportunity to cure it.
The cells of your body guard against cancer in a variety of ways scientists are only beginning to understand. A key element in these defenses are so-called tumor suppressors, proteins which actively prevent tumors from forming. Two of the most important are named Rb and p53.
Rb (named after retinoblastoma, the rare eye cancer in which it was first discovered) acts as a break on cell division, attaching itself to the machinery the cell uses to replicate their DNA, and preventing it from doing so. When the cell wants to divide, a growth signal molecule ties up Rb so that it is not available to act as a brake on the division process. If the gene which produces Rb is disabled, there are no breaks to prevent the cell from replicating its DNA and dividing. The control switch is locked in the ON position.
p53, the tumor suppressor protein sometimes called the Guardian Angel of the cell, inspects the DNA to ensure it is ready to divide. When p53 detects damaged or foreign DNA, it stops cell division and activates the cells DNA repair systems. If the damage doesnt get repaired in a reasonable time, p53 pulls the plug, triggering events that kill the cell. In this way, mutations such as those that cause cancer are either repaired or the cells containing them eliminated. If the gene that produces p53 is itself destroyed by mutation, future damage accumulates unrepaired. Among this damage are mutations that lead to cancer, mutations that would have been repaired by healthy p53. 50% of all cancers have a disabled p53 gene.
Cigarettes cause lung cancer because they damage these tumor suppressor genes. Fully 70%-80% of lung cancers, for example, have a mutant inactive p53 genethe chemical benzo (a) pyrene in cigarette smoke is a potent mutagen of p53.
In 1977, virologists discovered that adenovirus (responsible for mild colds) could not reproduce within human cells without a working copy of two virus genes dubbed E1A and E1B. For over 10 years, this finding wasnt appreciated, as little was known about Rb and p53. Only five years ago did researchers learn that the proteins encoded by E1A and E1B are the tools the adenovirus uses to sabotage the cells tumor suppressors, so that the adenovirus can replicate itself within the human cell. Inside a human cell, the virus E1A protein disables the cells Rb, allowing the virus DNA to use the cells machinery to replicate copies of itself. Meanwhile, the E1B protein inactivates p53. With the watchdog p53 no longer able to prevent the cell from replicating damaged or foreign DNA, the adenovirus is free to replicate.