Cancer is the result of a series of mutations. Cells are controlled by an accelerator and a brake, the researchers say, and cancer is the result of an imbalance.
On the cellular level, pathologists can watch the cells go through a series of steps: (1) Hyperplasia, or increased division (2) Dysplasia, or abnormal shape and orientation (3) In situ cancer, confined to boundaries such as the basement membrane and prostatic capsule (4) Invasive cancer, with a vascular blood supply and shedding cells into the lymph nodes and blood supply (5) Metastases, usually to specific sites, such as the bone for prostate cancer. (6) In prostate cancer, hormone dependence.
(See diagrams in Tumor Development Occurs in Stages and Invasion and Metastasis in Scientific American)
On the gene level, each step is the result of another mutation. Prostate cancer starts in the prostate epithelium, and develops through about 8 genetic hits, each of which destroys another gene, finally becoming metastatic. Each gene had been restraining a different step in growth and transformation.
Genes can be examined on the DNA level or on the protein level.
On the DNA level, genes for the accelerator or brake are turned off by mutations, usually deletions, additions, repetitions, or substitutions in the DNA sequence. There are switches that turn genes on and off. One switch is methylation--adding a methyl group to DNA can turn a gene off, and for example stop synthesis of an endothelin-1 receptor.
On the protein level, one important switch is phosphorylation--adding or removing a phosphate group to the tyrosine amino acid of an enzyme can turn the enzyme on and off. For example, HER-2/neu and PI3 kinase add phosphate groups to turn on cancers, while PTEN takes the phosphate off.
My stories are typically about one of those genes. Typically, researchers compare cells as they progress from one step to another. Suppose for example you have normal cells that grow in vitro until they touch, and then stop growing, so that they form a thin sheet one cell thick. Then suppose a mutation causes those cells to keep growing after they touch each other, so that they form a bulky mass instead of a thin sheet. Or suppose for example you take a pathology sample of normal prostate tissue and cancerous tissue from the same patient. Researchers can compare the chromosomes, mRNA, DNA, and proteins in the normal cells and the mutated cells, to locate the mutation and identify its function.
The genes responsible for cancer are usually divided into oncogenes and tumor suppressor genes--the accelerator and brake.
For more background, the best introduction is probably the September 1996 single topic issue of Scientific American, "What you Need to Know About Cancer". For a more comprehensive background, the standard textbooks are Campbell's Urology and DeVita's Cancer.
In one sense, my job is to write news stories that tell doctors what we've learned about cancer since this issue of Scientific American was published.
Here are some of my stories, which explain how scientists are getting a better understanding of the mechanisms described above.