Purified DNA, fluorescing orange under UV light, is extracted and used for molecular biology studies. This visualization of a single band of DNA aids in the isolation and extraction of the DNA for future molecular biology studies. Source: Mike Mitchell
Cancer has terrified patients and baffled medical scientists for a long time. Recently, however, a new level of understanding of this dread disease has begun to emerge. Scientific studies initiated using widely different approaches are now unexpectedly converging to provide a picture of the molecular basis of at least some forms of cancer--including colon cancer and melanoma. The resulting insights are certain to have an important impact on the fight against cancer.
Much of this progress has come from untargeted basic research that is aimed at learning how the cells in all forms of life function. One group of researchers was studying the life cycle common to all cells. These scientists knew that their studies were critical to understanding a central life process that operates in all animal cells and hoped that their findings might in some way become relevant to understanding the processes that lead to human cancer. For a decade, they isolated and characterized a group of proteins that interact in complex ways to form the central growth-controlling machinery inside cells termed the cell cycle clock. At the time, the implications of their work on human disease were totally unclear.
Two of the cell cycle proteins they studied, known only as p16 and p21, were first described in a scientific paper published in December, 1993. Within just four months, another research team, working independently, found an important and totally unexpected link between the p16 protein and cancer. This team, which had set out to study hereditary melanoma (a deadly skin cancer), found that gene that directs a cell to make p16 is often mutated (altered) in cancer cells, leading to its inactivation. The mutations can be seen not just in melanoma cells, but in cells of many other forms of human cancer as well. This indicates p16 plays a critical role in the molecular processes controlling cell proliferation; when p16 is lost, the control of cell growth goes awry, leading to the runaway proliferation seen in cancer.
This discovery complemented a similar, earlier finding which showed that another cell cycle controller, a protein termed p53, also plays an important role in human cancer, being found in mutant form in about half of human tumors. So important was this early discovery that Science magazine named p53 as its 1993 "molecule of the year." Strikingly, insights into the cell's growth cycle, which have now become critically important for understanding human cancer, originated from studies of the life cycles of yeast, clam, sea urchin, and frog cells.
Understanding the molecular causes of cancer--the triggers that lead to disease--can lead to the development of new weapons to fight its spread, including the development of novel therapies, new types of drugs, and the use of gene therapy to correct defective versions of growth-controlling genes present within cancer cells. The "road map" sketched by those conducting fundamental research on the cell life cycle will be there to guide researchers who are now beginning to develop these and other innovative approaches to cancer treatment.
Yet another fully unexpected convergence of unrelated lines of research occurred in 1993. Several groups of researchers were studying tumors from patients with a hereditary form of colon cancer. Their published papers describing certain DNA abnormalities in these colon cancers attracted the attention of other researchers who had seen similar abnormalities in the DNA of baker's yeast cells. The yeast cells showed defects in a cellular system--termed mismatch repair--that checks the yeast DNA for errors in genetic text, enabling the cell to repair and hence erase the errors. The yeast cells carried several defective mismatch repair genes. When the human counterparts of these yeast genes were isolated, they were found to be the culprits responsible for hereditary colon cancer. The work on yeast not only showed precisely how such genes operate, but also led cancer researchers directly to find otherwise elusive human genes, saving years of research time.
Finding these colon cancer genes will enable members of families at risk for the disease to take a genetic test that will indicate who among them should receive frequent presymptomatic screening for colon cancer. In addition, as is often the case with untargeted basic research, research on this mismatch repair system will have applications for understanding yet other diseases beyond colon cancer.