Newer Vistas ('Stargate')-Pathogenesis on CRPCa (HRPCa)-Dr. Bonkhoff (expert pathologist Berlin)

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Date Joined Dec 2008
Total Posts : 3149
   Posted 3/9/2011 7:30 AM (GMT -6)   

I labeled this 'Stargate' (LOL) as it is huge in the scheme of PCa history.


New Vistas (‘Stargate’) in Pathogenesis for CRPCa via pathologists like Helmut Bonkhoff

The value of excellent pathology cannot be overstated, Dr. Strum premier PCa authority has expoused critical thinking and analysis on PCa for years and way ahead of the general medical knowledge base on PCa. He has mentioned Dr. Bonkhoff as ‘The best PCa pathology doctor  in the world. You could have your PCa slides reviewed by anyone at any time, they stay good in the wax just about forever, they are usually stored for long periods, before being thrown out (maybe 10-15 yrs.), you could take possession of them by contacting your doctor (not a bad idea either). You may wish to possess them.

Here is a synopsis of an article by Dr. Bonkhoff titled:  From Pathogenesis to Prevention of Castration Resistant Prostate Cancer:

Background: Significant progress is understanding the molecular basis of CRPCa  still remains a lethal disease. Early detection and prevention of CRPCa may provide a new strategy to improve survival in patients diagnosed with PCa at risk to fail standard androgen deprivation therapy (ADT).

Methods: A review of pathogenetic mechanisms implicated in PCa progression toward cprca disease that  are detectable in hormone naïve PCa to define relevant therapeutic targets for prevention.   (now my words: in simpler words original pathologies can be analyzed via staining methods (chromagrin etc.) as to defining your at risk PCa genes in your particular PCa and personal genetic suseptabilitiy and knowing this information doctors do already know about which drugs can combat certain genes and target a therapy suited to the patients risk (instead of the shotgun approach of Lupron or whatever drug given as standard issue)  This is why the successes of CRPCa or HRPCa’s are done so well through the leading prostate cancer oncologists (Myers et al) but they are doing it usually without knowing this pathology background information. Thus they are artists in the world of PCa.

There are many pathways to effect the genes and receptors in PCa, Lupron and casodex and others work on certain levels, but in HRPCa (which can happen over time, we see some patients do well on ADT drugs for 2-5 yrs. and fail and others can go 10 years, this has to do with cellular issues on the genes and receptors and the cycles that happen, DNA (ploidy) of PCa can change over time, thus showing that a less aggressive cancer could in fact later get more aggressive or more resistant to certain therapies. Thus the introduction of various possible drugs and protocols to change what is happening on a cellular level. It is an art at this stage in PCa is my contention, although it is going to be come more of a science that is more reliable and this is what all this mentioned is about. Hormone naïve means the patient has not yet used ADT therapies, after using such in some cases the androgen deprivation when failed, your PCa cells can actually manufacture it own androgen and fuel PCa (weird as that seems) and this is why with HRPCa you find very often continuous PSA levels upwards even while on ADT drugs.

Some of the genes identified in PCa, most of these are unknown as to what their particular purpose actually is:  CPNE3, IL1b, CDH13, EHBP1, NUDT10, NUDT11, MSMB, LMTK2, KLK3, CTBP2, JAZ_

We already know about P53 gene in PCa and know about for breast cancers the risk factor genes called BRCa1 * BRCa2;  we may know about hormonal growth factor receptors HER-1, HER-2, we might have heard of BCL-2  mechanisms. Dr. Bonkhoff can identify many of these genes and we now have some  targeted drug interventions known to be effective upon those types of PCa that can be used…this information is available NOW but not through every pathology doctor, but some like Bostwick, Oppenheimer, maybe Epstein and others are following this lead of Bonkhoff more and more. Patients would have to ask and pay additional for these particular types of tests in pathology and in my estimation should do so asap…the information on your pathology is the key to knowing what genetic issues you may have to begin with for PCa..this info can be used or gleaned from the slides even 10-15 years later (which now could be huge info going forward). This same data might be useful in using Provenge or other future vaccines that are scheduled to be introduced, some in trials now  We should probably ask for ploidy analysis right now in pathology which Dr. Bostwick , Bonkhoff and maybe Oppenheimer have been doing for years and years. Some leading oncologists like Myers, Strum et al, have found this data useful in following patients with CRPCa/HRPCa and therapy interventions to use and perhaps when, based upon the patients history and pathogenisis. The wisdom of doctor Strum et al can never be overstated---knowing best assessment and the biology of the patient—leads to best tailoring the treatment to the particular patient. Per Dr. Barken the concept is maximum assessment, minimal intervention (as perhaps necessary) and maximum quality of life. These voices in PCa can never be heard loud enough, in my understanding of this.

Conclusions(Bonkhoff): CRPCa is the end=stage of a mutlifactorial and heterogeneous disease process. Pathogenetic factors respondsible for the development of the CRPCa phenotype are detectable in the patient’s PCa tissue long before the clinical onset of the disease. This approach provides opportunity for early detection and prevention by targeting pathways relevant for the individual disease process.

(My words)- PCa is far from simplistic as you might further comprehend just from this type of information. Strides are being made in vaccines, drug protocols and better original pathologies and assessments….all key things for more selective treatment and tailored protocols or modalities to treat your particular cancer. Since your original pathology is a major player in assessment as to Partin Tables, nomograms and similar current analysis and therefore huge part of decisions upon treatments, this kind of information is very important and going to become more important and more well known soon. Other pathologists will be into this wisdom more so within 1-3 years is very likely, mean while you can decide whom does your pathology and what types of additional tests you might ask about (call the experts directly), your slides can be sent or reviewed by them at any time. Your local average pathologist might not even know all that much as to why or what types of additional tests you might actually be well served in having or knowing. So, knowledge is power and patients knowing these things it is going to become more well known thanks to shared information and wisdom of doctors like Bonkhoff and leading oncologists whom work with CRPCa/HRPCa disease level patients, often.

Some may see better why I refer to PCa, sometimes as the Twilight Zone or living in Limbo Land with PSA’s being your guideline (but is not always accurate as to what is happening on the cellular level), even with a stabilized PSA number (in case you didn’t know you are not necessarily all safe, you need your oncology monitored).  Dr. Myers demonstrates in more recent video of a patient with low risk factors(clear biopsies) and stabilized PSA, but 4-5 years later with color Doppler ultrasound PCa was then detectable, where prior his biopsies were found clear, however the mans fPsa value was 17% (which is a clue that PCa is happening). Thus any data you can get on PCa can be valuable in the correct ‘experts’ hands. Best to all of us in this PCa journey.

Helmut Bonkhoff, MD, Pathology Laboratories  (Berlin, Germany)email:     

(off the internet)=One of the most promising recent breakthroughs may be the discovery of a susceptibility locus for prostate cancer on chromosome 1, called HPC1, which may account for about 1 in 500 cases of prostate cancer. The next step will be to clone the gene. Once researchers have the sequence, they will be able to search the databases to compare the HPC1 sequence to previously characterized proteins from both humans and other animals. This should provide clues as to the function of HPC1 in the cell, and suggest potential starting points to find drug targets.

(Hope you find this information useful and interesting, I know I do)

Post Edited (zufus) : 3/9/2011 5:45:47 AM (GMT-7)

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