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Seventh International Prostate Cancer Congress Turnberry Isles, Aventura, Florida July 27 – July 29, 2007 CONFERENCE REVIEW by David S. Most, PhD Health Information Research, Inc. North Palm Beach, FL INTRODUCTION… This Conference was produced and hosted by the P.E.R., the Physician Education Resource group. They plan and produce hundreds of conferences annually in all the specialties and sub-specialties of medicine. The structure of this conference was built around lectures and panel sessions on each of three mornings. Papers began at 8:00 AM and ran until 1:00 PM including Q&A panels after each group of three papers. Typically, 14 to 15 such events were planned for each morning. A very intense schedule that reduced time for meaningful Q&A FACULTY… Some 27 of the country’s leading prostate researchers in the fields of urology, radiology, oncology, and microbiology were among the presenters. An interesting observation by the author noted was that only some 10 of the 27 had no “conflicts of interest” to disclose. All seventeen others reported financial links to one or another or combinations of pharmaceutical companies. They were either consultants to, or on the Speakers Bureaus of, these corporations. The closer the presenter was to anything having to do with drug development, current and/or future, the more conflicts he or she reported. The urologic surgeons and most of the radiologists reported no conflicts. CONFERENCE OVERVIEW… The approximately forty five papers that were given ran the gamut from the introduction of a potentially more sensitive and reliable PCa indicator test to replace or supplement PSA, to some of the latest genomics research that is exploring the basic molecular biology of prostate cancer. Lecturers repeatedly discussed the heterogeneity of PCa as the most logical reason why drugs intended to deal with PCa often have such varied response rates. Typical trial results with new drugs may show that only 15-25% of participants had significantly positive responses while perhaps another 15-25% were only moderate responders. The balance of the participants may not have responded at all. Yet all were prostate cancer patients whose disease parameters had been measured and graded using the standard parameters of Gleason Score, PSA, T stage, DRE, etc. Despite being matched by these conventional parameters, wide variations in response to treatment can and do occur. The heterogeneity of prostate cancer is now being studied via genetic and microbiological approaches and these are likely to be productive approaches. Much more is now known about the “androgen receptor” role on the surface of the cell. Manipulations that affect this AR are being intensively studied. Second and third line hormonal manipulations are being studied to finesse the issue of androgen independent prostate cancer. Of interest was the discussion of circulating androgens that persist even when testosterone has been dropped to castrate levels. Despite the advances in knowledge that were discussed, the gap still exists between theory and practice: PSA progression after primary tx is still treated with androgen blockade therapy and introduction of new products is slow. SURGERY… In the area of new surgical approaches to prostatectomy it was reported by a leading surgeon from Memorial Sloan Kettering that “new” does not necessarily mean “better”. He is a surgeon who has done thousands of radical prostatectomies using the conventional “open” method and both laparascopic and robotic techniques. The latter two are the least invasive. His conclusion was that the total experience of the surgeon was more important than the method selected. And this conclusion was offered in spite of the enormous publicity about robotic surgery and its advantages. He showed data relating number of prior surgeries to five year biochemical failure rates. At least 500 surgeries were required to reach a plateau. Choose the surgeon, not the method, was his take-away message to the audience. RADIOTHERAPY… IMRT is the dominant form of radiotherapy today. Combined with improved methods for imaging the position of the prostate gland prior to irradiation, side effects are being reduced. Use of adjuvant and neo adjuvant hormonal blockade tx in conjunction with IMRT is beginning to show improvements in overall survival rates. It is worth noting here that rare was the speaker who discussed in any detail the extent of side effects from the various treatment modalities. Radiation side effects such as rectal injury, incontinence, and impotence were covered in some presentations. Changes in techniques that help reduce these effects were described. Chief among these is the increased use of “gold fiduciaries” implanted into the prostate to allow the technician to determine his target prior to each treatment session. It was emphasized that a patient planning to undergo external radiation should assure himself that the facility chosen has the most modern equipment installations and will routinely determine the gland’s position prior to each treatment. Proton beam installations are increasing around the country so we can expect to see more men select that as their primary tx. Because of its unique energy delivery system, proton beam theoretically should have fewer side effects. But, it was emphasized, radiation is still radiation and exposure of non-diseased tissue will still occur. CHEMOTHERAPY… The trend towards using Docetaxel (DT) as primary chemo for HRPC continues to accelerate. Despite the fact that only a 2+ month improvement in overall survival relative to Mitoxantrone and prednisone, was shown in the clinical trial that led to its approval, it has become the “standard” for chemo tx of advanced PC. Also, Satraplatin, a new form of platinum based chemo, has been shown to be effective. Recently, however, the FDA has requested additional data for Satraplatin so there is some uncertainty as to the immediate future. Reportedly, it will be back in the market as soon as the FDA’s request for more data has been satisfied. New drugs continue to be tested as last line tx for HRPC. Atrasentan was mentioned as one. But the data presented during the lectures did not produce any “Aha” moments vis a vis chemo in PC. In a private communication, a leading oncologist in the NYC region told the writer that this practitioner has pts undergoing 4th and 5th chemo regimens that are prolonging their lives. This Dr. was not reluctant to use chemo drugs that had not yet been approved for PC. Off label applications are limited only by the oncologist’s imagination and willing to experiment with the assistance of the pt. Take-home message for chemo regimens: DT is the primary chemo drug used today and DT in combination with other drugs are worth exploring. Provided the well known SE’s of chemo can be tolerated by the pt, life can be prolonged even in advanced PC. ADVANCES IN PROSTATE PATHOLOGY… Dr. David Bostwick, a world-renowned prostate cancer pathologist, spoke about the newest PC detection test called PCA3. It is based on a urine analysis preceded by prostate massage. It is a test with higher specificity than PSA but does require the services of a urologist to collect the test specimen. It is eleven years since it was first reported and only now is getting used by the physician community. It is a gene that is highly over-expressed in PC. Bostwick reported that PCA3, when positive, predicted a positive biopsy result in 75% of cases. If a man is scheduled for a PSA test, he should ask his Dr. to have the PSA3 test run. Since it has not yet been FDA approved, Medicare will not pay for it but in our opinion it is worth paying for out of one’s own pocket. It’s the same old mantra applied to this: THE EARLIER THE DETECTION, THE GREATER THE LIKELYHOOD OF CURE! He also discussed the use of a triple staining technique by the pathologist to increase the certainty of his/her tissue analysis. THE ANDROGEN RECEPTOR…. Much talk during the lectures centered on the critical role of the androgen receptors on prostate cells. These are the proteins that accept and admit into the cell, the male hormones that promote PC development and growth. The impact of the androgen receptors is: -AR activity confers risk for PCa -AR is essential for PCa in genetically engineered mice -AR controls PC growth and susceptibility of apoptosis -AR activity is essential at all stages and phases of PC (this summary was presented by Prof. E. Gellman, Columbia Univ.) He referred to the AR as “the oncogene of prostate cancer. It follows therefore that much research is being directed at this target by the pharmaceutical industry. Professor Gellman was identified as a major holder of Genentech and GSK stock. CONTINUED EMERGING CONCEPTS IN IMMUNOLOGY
In this session, the speakers discussed current status of vaccine programs and potential new immunologic approaches. Dr. Charles Ryan of UCSF discussed some early results of tests using CTLA-4 (Cytotoxic T-lymphocyte Antigen 4) as a T-cell activity booster in HRPC. It is also being studied in melanoma research. The approach being studied is to block the action of CTLA4 and thus activate “antigen specific T cell responses”. Phase I trials have shown results specific to immunological kinds of responses such as rash and fatigue. Increases in CD4+ activity were also observed.. A monoclonal antibody intended to affect the blockade of CTLA4 has been developed. It is called Ipilumimab and in single agent trials has appeared to be safe and active in a single dose study. Future studies being planned at UCSF with this product include testing it in combination with GM-CSF, androgen deprivation, chemotherapy, and vaccination with GVAX and APC8015. GM-CSF (granulocyte macrophage-colony stimulating factor) has previously been shown to be effective (see Leukine ® results) in lowering PSA in HRPC cases. Combining it with Ipilumimab will determine if any synergy exists with the combination. The preliminary results reported by Dr. Ryan are sufficiently encouraging to warrant further studies that are likely to be funded by the developer. THE CURRENT PROVENGE® STORY: Dr. Paul Schellhammer, President of the American Urological Assoc., reviewed the history of Sipuleucel-T, alias Provenge®. This product has been under development for several years beginning in 1999 by the Dendreon Company. It is one of the earliest attempts at developing a vaccine that might be effective against PCa. Since the vaccine is derived from each individual patient’s own serum, it represents an early attempt at a kind of “personalized medicine”. He showed some data obtained from clinical trials in which the time to disease progression was delayed some 8 weeks. Overall survival benefit reportedly was a median of 4.5 months. The FDA has ruled that more data is required before approval will be granted. Dr. Schellhammer believes that the FDA action was inconsistent with the Advisory Panel’s actual recommendations. He suggested that it was an “opportunity lost”. Prostate activists have been banding together to apply pressure to the FDA to OK this immunological process for general use. As of this writing, the Dendreon Company has additional studies underway to provide the additional data required by the FDA. NEW TRIALS AND CONCEPTS FOR PC VACCINES This was the title of Dr. Susan Slovin’s presentation. She is an oncologist/researcher at MSK in NYC and serves on the Speakers Bureau of Astra Zeneca, Novartis, and Sanofi-Aventis who are all active participants in the development of drugs for PCa. She set the background for her talk by discussing the elements that are needed to evaluate immunotherapeutic results. For instance, she reported on concerns that any given in vitro result may not correlate with a true antitumor response. She pointed out the need to properly identify the immunological tumor target. To illustrate the problem, she showed a slide with four possible clinical trial endpoints: Tumor responds target is hit Tumor responds target is missed Tumor doesn’t respond target is hit Tumor doesn’t respond target is missed These four end result scenarios illustrate some of the issues encountered in this kind of research. She discussed some results obtained with GVAX, a vaccine being developed by Cell Genesys. Some results were shown with this vaccine in combination with selected chemo drugs. The basic thrust of her talk was about the difficulties of defining what and how to measure immunological trial results. To deal with the complex issues mentioned above, Dr. Slovin discussed the formation of a new consortium of academia, industry, and govt. agencies to recommend immunologic endpoints for studies and also to develop lists of acceptable immunologic assays that can be used in future research. She also suggested that this consortium, PIGs (Prostate Immunotherapy Group) should ask the Dept of Defense to implement more immunotherapy research into its special prostate research program funded by Congress. The PIGs membership contains is a roster of who’s who in prostate cancer research: MSK, U of Wisc., Johns Hopkins, UCSF, Northwestern, MD Anderson, Cornell, Prostate Cancer Foundation and others. The take-away message from this talk was that it is early in the immunologic therapy and further developments with practical applications are still some time awayl,. TREATMENT RELATED OSTEOPOROSIS This session was devoted to issues of bone impact of PCa itself and of the hormonal blockade therapies used to control HRPC. Dr. Mathew Smith, of Mass General Hospital oncology chaired the session and presented a couple of the papers. Dr. Smith reported being a paid consultant /Advisory Board member for Amgen, Genentech and Novartis. Some of his research funding comes from Amgen and Novartis. He defined the osteoporosis problem for men in the USA with these stats: -2 million men in USA have osteoporosis -8 million men in USA have osteopenia 1 in 4 is lifetime fracture risk for men over 50 The direct costs for these bone conditions is > $3 billion annually! He listed as the primary causes for acquired osteoporosis: alcoholism, chronic glucocorticoid therapy, and hypogonadism. With the greatly increased use of LHRH agonists for reducing testosterone in men dealing with HRPC we are seeing rapidly growing numbers of men with bone issues. To put perspective on the issue, Dr. Smith referred to a paper by Barry, et. al. in the 2006 edition of the BJU International. These data showed that as the frequency of orchiectomies has declined (1993-2000), there has been a parallel and even more dramatic increase in the use of androgen therapy in the USA. The heavy usage of LHRH agonists has contributed dramatically to the overall decline in bone mineral density seen in an increasing percentage of men in the USA. Not only is the issue of bone mineral density coming to the fore, but the change from muscle to fat tissue is a major issue. Men being treated with LHRH agonists to suppress androgen and slow tumor growth encounter major side effects that alter quality of life dramatically. In all cases of men on LHRH treatment, the relative risk for fractures of all kinds increases significantly; from a low of 1.25 for “any fracture” to a high of 1.63 for vertebral fractures. Or in layman’s terms, the risk is 25% greater for any fracture while for vertebral fractures, it increases by 63% with hip and femur fracture risk increased by some 46%. Smith showed data (Michaelson, JCO 2007) using Zoledronic acid (Zoledex®) in the prevention of treatment related osteoporosis. These data showed a dramatic increase in BMD compared to placebo in the men treated with the Z after 12 months. Similar effects were shown for all of the currently available bisphosphonate products. He showed additional studies of Raloxifene® and Toremifene® indicating that these SERMs (Selective Estrogen Receptor Modifiers) also help to prevent osteo problems by reducing the overall bone mineral density losses caused by ADT. Despite the negative statistics quoted above, Dr. Smith reported that ca. 50% of men do not get osteoporosis absent LHRH treatments. Dr. Oliver Sartor, Dana-Farber Oncology, Boston, Mass talked on the subject of “Stromal-based Bone-Targeted Therapies: Radioisotopes”. He is a paid consultant/Advisory Board member of Cytogen, Dendrion, GPC Biotech, Glaxo Smith Kline, Novartis, Roche and Sanofi-Aventis. He receives research funding from Glaxo Smith Kline, GPC Biotech, and Sanofi-Aventis. Dr. Sartor discussed his and other’s work using products such as radioactive phosphorous, strontium, samarium, rhenium, tin, and radium. The overall mechanism of action of these radiopharmaceuticals is the targeting of PC metastases in bone. Dr. Sartor illustrated the palliative effects of stromal targeted therapies and then discussed the directions that may be taken to modify or improve these treatments for improving survival. Among the strategies he suggested were: -Repetitive Dosing? -Different Doses of currently used isotopes -Combining isotopes with other known effective therapies -Alternative isotopes or targeting strategies -All the above? Specifically, Dr. Sartor suggested that treatments which combine Samarium, for example, with Docetaxel gave improved results. Work by Widmark, et. al. (ASCO 2006) showed significant PSA declines in 34% and 21% of men depending on specific protocol. However, the improvements were not long lasting because they reported the median time to PSA progression was 126 days and to clinical progression some 108 days. The takeaway message from Dr. Sartor’s talk was essentially that palliation is achieved with radioactive isotope therapies and combinations of these with cytotoxic agents do produce better results. No dramatic breakthroughs have been achieved. We can expect to see an ongoing stream of clinical trials using the approaches listed in the “strategies” table above. OSTEOCLAST-TARGETED THERAPY….BONE METASTASES This was another presentation by Dr. Smith addressed to targeting of the bone attacking osteoclasts that are a significant component in the whole metastasis process in advanced PCa. He reviewed some of his own published work on the effectiveness of zoledronic acid in the moderation of bone mets in advanced PCa. He showed how the drug reduced the marker for osteoclast activity and reduced the cumulative index of skeletal related events. He also discussed some early work on Denosumab, a new monoclonal antibody that has shown some effectiveness in bone metastasis in breast cancer. This material acts via a different mechanism than the bisphosphonates. It is an Amgen developed product and Dr. Smith is a consultant to and member of the Advisory Board of Amgen. Barring any untoward side effects being revealed in ongoing trials, we are likely to hear more about this approach to bone mineral density improvement. NEW DATA WITH CHEMOTHERAPY/RADIOISOTOPIC COMBINATIONS Dr. Michael Morris of MSK GU oncology dept. presented this lecture. He reviewed some recent work with combinations of Docetaxel and Samarium 153 in pts with bone mets. Early results are encouraging with this combination in phase I studies. Accrual for phase II study is underway. The individual toxicities from each drug did not appear to be enhanced by the use of the other. In the Panel session that followed this paper, Smith and Morris agreed that Docetaxel is the current best chemo drug for advanced HRPC. Also, bone mineral density is a good surrogate for fracture risk. Some kidney related side effects have been reported among pts. getting Zoledronic annual injections. ACTIVE SURVEILLANCE: HAS THE TIME ARRIVED This session of papers dealt with one of the most important issues in PCa today: are men being over treated for prostate cancer? Are our PSA testing and screening procedures leading to men being unnecessarily treated and consequently having their quality of life impacted negatively? Can men with low grade tumors simply be monitored and treated later, if necessary? Dr. L. Klotz, Professor of Surgery at Univ. of Toronto and Chief of Urology at the Stoneybrook Health Sciences Centre was the leadoff speaker. He is a consultant to and on the Advisory Board of, Abbott Labs, AstraZeneca, GlaxoSmithKline, Sanofi-Aventis. He is also on the AstraZeneca Speakers Bureau. Professor Klotz made the argument that we are over-diagnosing prostate cancer and treating too many men who could lead normal lives for some years with either delayed treatment for PCa or who would die of other causes. These men would be spared the consequences of treatment side effects which can range from incontinence (mild to severe), impotence (from mild to total), and others less negative in terms of QOL. He identified as “favorable risk” disease parameters: Gleason Score < or = 6 PSA < or = 10 Number Pos. Cores < or = 1/3 Tumor in Cores < or = 50%, all cores In addition to these criteria, he showed how he adjusts for age. For younger pts whose life expectancy is greater to begin with, he suggested “more stringent pathologic criteria”. But for men over 70, Professor Klotz is willing to use more “relaxed” criteria, e.g., PSA > 10 and even some Gleason components of grade 4. But to cover the balance of the intangible diagnostic criteria, he adds “Clinical Judgement”. He also discussed some of the newer published data showing the importance of PSA kinetics in determining risk of relative aggressiveness in a pt. He recommended that PSA DOUBLING TIME is more useful than PSA velocity. The balance of his talk dealt with some published data that discussed results with various cohorts of men over a wide range of disease parameters. For example, he reported on a small trial with 38 men. This trial compared results between a group who were given active surveillance vs another group who had immediate RPs (Warlick, et. al. JNCI 2006:98(5) 355. The median time to RP in this group was 26 months. Klotz reported that there was no difference in the risk of disease progression. He also discussed some of the psychological aspects including mens’ fear of “the cancer” in his body. But because PCa is mostly associated with older men, there is a greater probability of a man dying from another cause than from his PCa. A Phase III randomized clinical trial is currently recruiting pts. The study is titled “Surveillance Therapy Against Radical Treatment (START) in Patients diagnosed with Favorable Risk Prostate Cancer”. It was supposed to have started in 2Q of 2007 but at the time of this lecture, hadn’t begun. [Ed. Note: The major risk in this approach is that the diagnostic tests available to determine relative aggressivity are still lacking in selectivity and specificity. PSA by itself is too subject to non-cancer related influences, Gleason Score although quite good, still cannot distinguish between a dangerous GS = 6 and a less dangerous but still GS 6 tumor. More precise methods of quantifying PC risk are still needed.] FOCAL THERAPY: NEW APPROACHES AND CONCEPTS This lecture was delivered by Professor David Crawford of the Univ. of Colorado School of Medicine. Dr. Crawford had no corporate financial conflicts to report. He was one of the very few without support of corporate money. Dr. Crawford agreed with Dr. Klotz about what constitutes “low risk” PCa; PSA ,<= 10, GS <=6, and State T1c-T2a. Using Dr Stamey’s long term data, he indicated that prostate volume correlation with prostate cancer diagnosis has dropped from 0.68 to 0.12 because of “volume migration”. That is, PSA has found more cancers earlier than ever before therefore the volume of tumor found will also be lower. Today, Dr. Crawford reported that his average pt. is 59 YO, PSA 5 – 6, GS =6, with 1 or 2 cores showing 5-10% tumor. He cited some of Dr.Klotz’s data supporting active surveillance but came down on the side of focal treatment based on saturation biopsies. This methodology requires what he called “mapping” biopsies to determine where and how many focii of PC were present. He argued that with current new technology (i.e., cryosurgery) focal therapy can treat PCa early and avoid the major QOL side effects that normally follow RP or RT treatments. The normal options he listed for localized prostate cancer are: -Watchful waiting -Targeted Therapy -Active Surveillance -Definitive Therapy (surgery or radiation) -Hormonal therapy Out of this list he chooses targeted therapy because: -It provides an efficacious and cost effective curative alternative to RP and RT with fewer complications (ED, incontinence, rectal injury). -Shorter time of procedure (cost efficacy) -Improved patient satisfaction and QOL His rationale behind this “targeted approach” is based on the following: -A vast majority of currently newly diagnosed PCa appears to be organ confined. -Many pts are interested in minimally invasive options in treating their early stage disease with fewer side effects without compromising cure rates. -But finally, “NO TREATMENT IS GOING TO MAKE YOU A BETTER MAN THAN YOU ARE RIGHT NOW”. [caps added] The U. of Col. Independent Review Board approved his trial protocol with the Primary objective being: “To determine the feasibility of using targeted focal therapy as a primary treatment for organ confined prostate cancer. The Secondary objective was to “assess the side effects-incidence of urinary incontinence, rectal and urethral injury and erectile disfunction (ED). Given the current limitations of adequately determining the true risk of a given PC and the difficulty in locating all of its focii within the gland, Dr. Crawford comes down on the side of focal ablation with cryosurgery. And it should be mentioned that Dr. Crawford has been a widely known and respected urologic surgeon for many years. The balance of his lecture dealt with the present lack of good imaging methods for identifying tumor regions within a gland and the risk of not finding all the focii of tumor even with “saturation” biopsies. CONTINUED... NOVEL APPROACHES TO FOCAL THERAPY… Professor John Trachtenberg, Chair of Prostatic Disease, Professor of Surgery, at the University of Toronto delivered this lecture. He indicated no financial connections to the Drug Industry. He reviewed the frequent morbidity that accompanies conventional prostate primary therapy of the several kinds currently in use. He came down on the side of focal therapy approaches when diagnostic information indicates a high probability of successful results from this ‘male lumpectomy approach’. Dr. Trachtenberg reviewed the diagnostic parameters that would allow a physician to conclude that the pt was a candidate for local therapy. These were essentially as indicated by the previous speakers: low volume of disease, Gleason score of 6 or less, PSA < 10 with a slow doubling rate, etc. These types of cancer would be the same ones that Professor Klotz in an earlier paper suggested were the best for “Active Surveillance”. Trachtenberg disagreed with Prof. Klotz because, he argued, there is too much uncertainty in presently structured biopsies. He made the point that “Low risk is not NO risk”. And given enough time, “Low risk can become REAL risk”. “There is uncertainty in our ability to predict individual outcomes by any method.” So given these significant levels of uncertainty connected with either what used to be called “watchful waiting” or what is today called “active surveillance”, there is a very real need for a therapeutic approach that can be applied to low grade disease without incurring any of the heretofore accepted morbidities of incontinence, impotence, rectal damage, etc. He then described an approach being developed by him and associates at the Princess Margaret Hospital in Toronto that utilizes the Indigo® Laser System in combination with an MR guidance system to perform “male lumpectomies” in low risk patients. To conclude his lecture he described the results obtained on a 62 yo man with “low risk” PCa who wanted some kind of “active” treatment in lieu of watchful waiting or “active surveillance”. Immediately following the procedure he had normal continence, normal potency and normal urinary and bowel functions. Professor Trachtenberg concluded by making a strong argument that this kind of less-than-massive-morbidity inducing procedures is the wave of the future and can likely be applied to other tumors than prostate as effectively. Because of the associated MR and other imaging methodologies involved, this approach is not going to appear in other urology clinics any time soon. He identified and thanked a large team of some 20 people involved with the development. To any man interested in dealing with his “low risk” PCa, he should follow this development as it moves into wider application. CLINICAL TRIALS REVIEW- COOPERATIVE GROUP UPDATES This portion of the program involved presentations by active research clinicians On currently active clinical trials for prostate cancer. There were reviews of radiotherapy trials, new chemo drug trials, and miscellaneous others. The interested reader should go to the web site for the NIH where he/she can find a detailed listing of NIH sponsored trials and the sites where they are being conducted. For trials being funded by the drug companies, either see their own web sites or one of the sites that attempts to collect all of them by type. During the Panel session that followed this group of presenters, it was disclosed by Dr. Daniel Petrylak, that some pts on Docetaxel have stayed alive out to 5 years. And some 70% of Docetaxel users are still alive after three years. This is the chemo regimen that has been specifically approved for PCa by the FDA. MOLECULAR PROGRES IN THE CLINIC VIRAL ONGOGENESIS AND GENETIC ALTERATIONS… This opening lecture was presented by Dr. Eric Klein, Professor of Siurgery and Head of the Section on Urologic Oncology at the Cleveland Clinic in Cleveland, Ohio. His subject was the XMRV virus as a possible cause of prostate cancer. It was described as a “novel pathogen” that had to infect man much earlier than at the time of cancer diagnosis. Professor Klein discussed the key postulates that have to be met in order to establish that this virus could induce prostate cancer: Koch’s Postulates -Organism must be regularly associated with the disease and its characteristic lesions [he said that it was] -Organism must be isolated from diseased host and grown in culture [has been done] -Disease must be reproduced when organism introduced to susceptible host [planned for future primate studies] -Organism must be re-isolated from experimentally infected host [planned for primate studies] As this time, Dr. Klein stated that much more work remains to be done before it can be conclusively stated that XMRV is a major factor in creating prostate cancer. Dr. Klein did not report any financial conflicts. STEM CELLS – NEW CONCEPTS AND THERAPIES Dr. Reiter is Professor Urology and Molecular Biology at the UCLA Geffen School of Medicine in Los Angeles, CA. He had no financial conflicts to disclose. The formal title for this paper was “Stem Cell Antigens as Therapeutic Targets in Prostate Cancer”. The hypothesis behind this work was reported as: CANCER STEM CELL HYPOTHESIS - Cancers arise from transformation of stem/progenitor cells. - Cancer stem cells can self renew and give rise to differentiated progeny - Cancer stem cells are tumorigenic whereas progeny are not - Cancer stem cells should be targeted therapeutically to improve results of anti cancer therapy. The rationale behind this line of research is to develop antibodies that would recognize these PSCAs and attack them. To this end he discussed some early research results with antibodies known as 1G8 and a humanized one (as distinct from the mouse model) called 2B3. Dr. Reiter indicated that Merck was supporting their work to develop another antibody identified as MK-4721. This was a good example of the kind of basic research that occurs in some laboratories that take longer range views of the problem. Such basic research will one day allow us to understand the root causes of cancer and then to develop a whole new generation of targeted drugs that can selectively “hit” their targets and reduce cancer burdens.
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