Isoflavone-derived drug inhibits prostate tumor metastasis
The Ninth Annual American Association for Cancer Research Frontiers in Cancer Prevention Research Conference held November 7 to 10, 2010 in Philadelphia was the site of a presentation by Raymond Bergan, MD of Northwestern University concerning the development of a pharmaceutical agent based on the soy isoflavone genistein which could help prevent the metastasis of prostate cancer. While localized prostate cancer has a very high rate of treatment success, disease that has metastasized to other areas of the body has a much poorer prognosis.
In a phase II study implemented by Dr Bergan and his associates which involved the administration of genistein to men with localized prostate cancer prior to surgery, an increase in the expression of genes that suppress metastasis and decreased expression of genes that enhance it were found in the prostate tissue of subjects that received the compound. "This is the first time that it has been possible to inhibit prometastatic pathways in humans by targeted therapeutics for any cancer type," the researchers announced.
Acting on these findings, Dr Bergan's team sought to develop a new drug with improved efficacy and high specificity. The compound they developed, known as KBU2046, has greater anti-invasion efficacy compared to genistein, while lacking the potential for estrogenic activity.
“The first step is to see if the drug has the effect that you want on the cells and the prostate, and the answer is ‘yes, it does,’” stated Dr Bergan, who is the director of experimental therapeutics at Northwestern's Lurie Comprehensive Cancer Center. “All therapies designed to stop cancer cell movement that have been tested to date in humans have basically failed because they have been ineffective or toxic. If this drug can effectively stop prostate cancer from moving in the body, theoretically, a similar therapy could have the same effect on the cells of other cancers.”
"We are in the process of bringing KBU2046 into the clinic, with the goal of preventing death from the second most common cause of cancer related death in men," the researchers conclude.
Once a diagnosis of prostate cancer (PC) is established by means of tissue biopsy and microscopic findings showing PC, the foundation of the medical record should have further information added to it to allow for an even greater understanding of the patient's true status. In this context, status refers to the actual extent of disease, or stage of disease. Is the PC really confined to the prostate gland or does it penetrate the capsule of the prostate or perhaps invade local surrounding tissues such as the seminal vesicles and nearby lymph nodes? Are there any clues that the PC has spread or metastasized to more distant lymph nodes or bone?
The orientation of most specialists will be toward recommending a local therapy to eradicate PC within the gland. This is the essence of the reasoning behind the surgical removal of the prostate—radical prostatectomy (RP). The other approaches toward treating PC with curative intent may be slightly more regional, but most are still designed to primarily treat the prostate gland. For example, external beam radiation therapy (EBRT) will include not only the prostate gland itself, but also a margin around the gland to kill any tumor cells that may be in this area trying to escape and spread to more distant sites. The same is true for the iceballs created by cryosurgery. The critical concept here is that local measures treat local disease. The determination of the true extent or stage of the disease is one of the critical variables in the strategy of successful treatment of PC. For example, if the disease is present outside the prostate gland in tissues such as the seminal vesicle or nearby regional lymph nodes (the obturator or internal iliac lymph nodes), an RP will have a significantly diminished chance in curing the patient with PC. The same is true for radiation therapy (RT) or cryosurgery. For such therapies to have a great chance of a cure, the cancer must be within the scope of the scalpel, within the boundaries of the radiation ports of therapy, and within the periphery of the iceball(s) created by cryosurgery.
An additional limiting factor for radiation therapy and cryosurgery is the amount of PC. The tumor volume has a bearing on the ability of RT or cryosurgery to destroy the entire tumor mass. This second variable in the equation may relate to the penetrating ability of the radiation particle used (photon < proton < neutron) or to the understanding that the core of a large tumor has a diminished oxygen supply (a hypoxic center) that confers resistance (called radioresistance) to the treatment. This actually may not be as critical a factor in cryosurgery as it is in RT.
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