(Image from: Models of the metastatic process)
Physicians have long been aware that the presence and number of metastases is a direct predictor or both short and long term mortality in cancer patients. Since the presence or absence of metastasis is thus the most important factor in predicting the “treatability” of any form of cancer, it is of great importance that cancer be diagnosed before metastasis has occurred. The early diagnosis of cancer, which is to say prior to metastasis, is desirable for three reasons:
1. To increase the probability of diagnosis prior to spread.
When cancer is detected prior to the development of metastasis, surgical removal or other such direct procedures as cryotherapy will result in a “cure rate” of 100%. However, the detection of metastatic disease by visual inspection alone is known to be inadequate. This fact has led to intensive research in the use of “markers,” such as genetic analysis and biochemical testing, to detect both metastasis and the potential of primary tumors to produce metastatic lesions.
2. To decrease the amount of therapy required, and
The number of cancerous cells present is called the “tumor load.” Obviously, the greater the tumor load, a greater the amount of a particular therapeutic agent (e.g. chemotherapy or radiation therapy) will be required to destroy the cancer cells. Unfortunately, all such anti-cancer therapies will have the potential to affect other, healthy cells as well. Since these undesirable effects are usually “dose-dependent,” it is desirable to administer the minimum amount of a particular agent that is sufficient to destroy the cancer cells yet minimize damage to healthy non-cancerous cells.
3. To decrease the likelihood that therapy-resistant cell lines will develop.
Everyone is probably familiar with the fact that bacteria and other pathogens have a propensity to develop a resistance, or decreased susceptibility, to a number of antibiotics. In a similar vein, tumor cells that are less sensitive to chemotherapeutic drugs will live slightly longer than their more-susceptible counterparts. When these less-sensitive cells divide, their “daughter” cells will inherit that resistance and, over time, a new therapy-resistant cell line will emerge. These new cell lines are a major factor in the failure of many anti-cancer regimens.
As noted previously, there is a great deal of interest regarding the use of genetic and biochemical markers in the early detection of both primary tumors and metastatic disease. The most familiar genetic marker currently in clinical use are related to breast cancer and mutations of the BRCA1 and BRCA2 genes, while the more familiar biochemical markers of cancer are the Prostate-Specific Antigen (PSA) in prostate cancer and the Carcinoembryonic antigen (CEA) , which may be detected in the blood of those with colorectal cancer.
The BRCA1 genes and BRCA2 genes provide the genetic code that produces certain proteins that either repair or destroy defective DNA during cell division. Clinically-detectable mutations in these genes are known to carry an increased risk of breast cancer and the amount of their associated proteins present in the bloodstream are under active investigation in the potential detection and therapeutic management of that condition.
At this time, the use of biochemical markers in cancer is hampered by issues of non-specificity and non-sensitivity. As an example, the Prostate-Specific Antigen is elevated in prostate cancer. However, it is also elevated in both acute and prostatitis as well, making it a poor indicator of the presence or absence of prostate cancer. By the same token, the absence of an elevated blood level of the Carcinoembryonic antigen does not preclude the presence of colon cancer and this marker may be elevated in cases of colitis and thus yield a false-positive result when used as a cancer screening examination.
In conclusion, this brief essay has reviewed the importance of early detection of both cancer and its metastatic component. Although at this time the use of genetic and biochemical markers in diagnostic and therapeutic strategies is still evolving, these areas exhibit considerable potential for future refinement.