The prostate is a gland the size of a chestnut, located under the bladder, encasing the urethra. Prostate function is to make molecules essential to sperm fluidification and fertilizing power.
The prostate is a gland that lifelong is subject to periods of growth. This growth is at the origin of a very common pathology beyond a certain age, benign hyperplasia of the prostate or BPH, resulting from the increase in size of the prostate which then compresses the urethra and causes urinary disorders. This pathology is not a cancer or a pre-cancerous condition.
Androgen and androgen receptor
Androgen, testosterone and dihydro-testosterone or DHT are major hormones male, produced mainly in the testicles. They play an essential role in the prostate.
A complex hormonal mechanism, initiated in the brain, controls the synthesis of testosterone.
Androgens exert their action by very specifically binding to a receptor, like a key entering a lock. Once both partners are linked, they penetrate into the cell nucleus and attach to the DNA of certain genes, which triggers the expression or the extinction of their expression.
Thus regulated genes encode proteins involved in many cellular functions, in particular the division, cell death (apoptosis), migration or relations of cells with their environment. All of these genes are regulated by androgen receptor, which is thus regarded as the “master gene” in the prostate.
One of the genes regulated by androgen receptor is well known because of its diagnostic utility: the Prostate Specific Antigen (PSA). Protein exclusively produced by the prostate, PSA is an enzyme that is secreted into semen to fluidify it. It is normally undetectable in the blood. Benign pathologies, such as inflammation of the prostate or BPH, or more serious, such as cancers, increase the production of PSA which becomes measurable in the blood. The PSA is a marker used by physicians to detect prostate disease and monitor the effectiveness of treatment.
Prostate cancers occur only exceptionally before the age of 50. The number of affected individuals increases with age. The disease usually progresses more slowly in aged individuals, so that beyond 75 years, patients dies more often with prostate cancer than because of prostate cancer. Depending on the age, the degree of advancement of the disease, the general condition of the patient and in consultation with him, the clinician chooses the most appropriate therapeutic tools among active surveillance, surgery, radiotherapy, brachytherapy, hormone therapy and chemotherapy.
When a prostate tumor is localized and low-grade, the standard treatment is usually active surveillance, surgery or radiotherapy. The blood PSA level is used to track the progression of the disease. It measures the activity of the androgen receptor in cells.
Just like normal prostate cells, cancer cells depend on androgens for proliferation and survival. Removing androgens causes their death. This fundamental discovery, which earned the Nobel Prize to Charles Huggins in 1966, allowed to develop treatments for these cancers.
More aggressive tumors are generally treated by androgen depletion or androgen antagonists. In animals androgen depletion is obtained by castration. Humans are given drugs that interfere with the production of hormones in the testes, or androgen antagonists that prevent the binding of testosterone to its receptor. They block the androgen receptor activity resulting in a decrease in the blood PSA concentration, and a regression or stabilization of the tumor mass.
However, different mutations can affect the androgen receptor. The receiver then becomes active (regulates its target genes), even in the absence of hormone. Disease relapses, PSA rises again. Treatment offered to patients at that stage is chemotherapy, which is given also in other types of cancers.