Saturday, March 23, 2013


In a man, there is a 1/3 chances that if found with cancer, it will be prostate cancer.  But only in 10 percent of those who are dying and who have prostate cancer is it this cancer that causes death.  Meaning a number of patients with prostate cancer will die of another cause.   Over 186,000 men were diagnosed with Prostate Cancer and close to 29,000 died of this disease yearly. A 6.5 to 1 ratio.  This point to a heterogeneous disease, and we will fail by not stating (infamous statement) that autopsy showed that in men over 80 years of age, over 70% will be found with Prostate Cancer.  As if it was part of aging.   By aging, you implicate Telomeres and most likely the MTOR.
Before jumping to the MTOR which is cool lately, there is one overwhelming phenomena, that is the Prostatic cell development is significantly dependent on Testosterone for its growth.  And we have in our armamentarium many agents to stop Testosterone.  As we will suggest and as achieved for many hormones, Testosterone blockage can be completed at the cell level, in the testicles, in the Adrenal gland as well as by blocking it in the Pituitary stalk. It is not until one develops refractoriness to Androgen that one may die of Prostate cancer as the principal cause of death.  So the physician's task is to keep coming up with new strategies to block the Androgens.  There lies the key to treating Prostate Cancers.

It is widely accepted that a small numbers of cells in the prostatic cancer mass (may be less than one percent at onset) will be mutated or spontaneously refractory to Androgen.  As time goes by, more mutations related or not to treatment, will occur, while hormone sensitive cancer cells are being starved from stimulation.  Over time, the refractory cells will grow in importance and drive the life of the tumor and metastasize everywhere replacing the hormone sensitive one. The disease will therefore become non responsive to Hormone and here comes patient rapid deterioration as the malignant tumor now adopts a new pattern of behavior including new locations of metastasis.  Liver lesions, lung lesions and Brain invasion becomes more likely to occur.   Chemotherapy with Taxane and Cabazitaxel, a derivative of natural Taxoids, become the mainstay of treatment.  ( Particularly now that Sipuleucel-T  is advanced to before chemotherapy) Keeping in mind that the reversal of fortune is change of proportions, there is still a portion of hormone responsive cells and Lupron needs to continue while chemotherapy is given!

PSA, Prostate Specific Antigen
Prostate cancer is actually one of the rare diseases that can be screened effectively, and found early by a blood test.  That is until we realize that finding a disease that may not kill early leads to unnecessary treatment and patient futile mental disturbance in many cases.  We are now retracting, pulling back on our toes and people are growing reluctant to be tested. That is until we clarify what it is we should be looking for to make sure we discern who needs therapy! We needs to know who needs an early intervention.  For this the tumor needs to tell us I am bad, and we need to catch the message.  And most researchers believe Genetic profiling is one of the critical approaches  to tell the difference. The challenge is that Adenocarcinoma seems to follow a progression in their deterioration to a full blown cancer.  And some genes are present in prostatitis, Benign Prostatic hypertrophy, Low Gleason prostatic cancer and high gleason cancers.   Now which one makes it a bad cancer.  This is the current challenge but it will clearly open the door to Target therapy!

Molecular basis of Prostatic cancer Pathogenesis.

While dealing with Intraepithelial Atypical lesion, the presence of Alpha-Methylacyl-Coenzyme Aracemase is considered a signature of Adenocarcinoma presence!   In our discussion on Choriocarcinoma, we suggested that Hypermethylation is a major Knockdown way for E2.  It plays a role here too!   And gene fusion is the other abnormality that is a prominent phenomenon TMPRSS2 and ETS fusion (or TMPRSS2-ERG), and things" degenerate" from there !

Also note that the Androgen receptor gene is located on Xq11-13, (note the "q")

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