Prostate cancer: where are we?(Disease/Disorder overview)

In this editorial review, I will provide an overview of prostate cancer. The specific areas I will discuss include the biology of prostate cancer and its prevention; the staging, early detection, and watchful waiting of prostate cancer; and the various therapies used to combat it--radical prostatectomy, radiation therapy, hormonal therapy, and chemotherapy.

BIOLOGY OF PROSTATE CANCER

The tumorigenesis of prostate cancer parallels that of virtually all other tumors. In this process, predisposing genetic risk factors combine with a variety of environmental factors, which leads to the initiation of the tumor and to its progression. As with most cancers, dysphasia eventually progresses to invasive carcinoma, metastatic spread, and androgen-independent cancer.

Many models have been created to explain the development of prostate cancer. The classic paradigm at a molecular genetic level is similar to that described by Vogelstein for colon cancer. According to this model, as normal prostatic cells move through the histologic transition to the development of locally invasive disease, cells experience chromosomal loss in a variety of areas: areas that express important cell adhesion molecules and areas that encode enzymes that restrict the unregulated growth of cells. In addition, there may be overexpression of other signaling molecules that leads to cell growth.

Another series of events causes those cells, which have developed into localized disease, to transcend that local environment. For this to occur, cells must develop motility. They do this largely by producing enzymes that degrade the basement membrane to allow cells to gain access into the lymphatic and vascular system. These cells maintain their ability to respond to androgens throughout all of these stages, but at some point between this step and the development of androgen-independent cancer, they acquire growth regulatory pathways that are not androgen-independent.

While theoretically and at a macro level this stepwise progression is well outlined, we still do not know the essential events that occur in the development of invasive prostate cancer. We do know the disease has a genetic basis. The familial risk of prostate cancer is actually higher than that for colon or breast cancer. Even so, only about 10% of all cases of prostate cancer can be explained on the basis of inherited risk.

Although androgens are essential for the regulation of normal prostatic function and the secretion of prostatic fluids, and although the withdrawal of androgens leads to programmed cell death, we do not fully understand their role in the development of prostate cancer. Clearly, androgens do not cause prostate cancer. But, on the other hand, prostate cancer does not occur in their absence. Androgens activate a series of enzymes that prevent programmed cell death, and increasing evidence points to defects in the apoptotic pathway as responsible for the development of androgen-independent prostate cancer. We do know that androgens do not fuel the growth of cancerous cells; a variety of growth factors and other signaling processes inside cancer cells themselves leads to their proliferation.

Research continues to provide new information about the biology of prostate cancer. But so far, we have not been able to take advantage of that knowledge to design specific therapies for the management of prostate cancer. Perhaps the 3 most exciting areas for potential treatment modalities are 1) the development of drugs to address what has gone wrong in the wiring of prostate cancer cells (cell signaling); 2) the repair of problems related to adhesion of individual cancer cells; and 3) the development of targeted therapy to interfere with the …