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UROSCAN |
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| Year : 2010 | Volume
: 26
| Issue : 2 | Page : 320-321 |
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Tackling the prostate cancer: Moving in the right direction
Bhupendra P Singh, SN Sankhwar, A Jain
Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, UP, India
| Date of Web Publication | 12-Jul-2010 |
Correspondence Address:
Bhupendra P Singh
Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, UP
India
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
Singh BP, Sankhwar S N, Jain A. Tackling the prostate cancer: Moving in the right direction. Indian J Urol 2010;26:320-1 |
Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR. XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. Proc Natl Acad Sci USA 2009;106:16351-6.
 Summary | |  |
In this study authors analyzed 334 consecutive prostate resection specimens (233 prostate cancers and 101 benign controls), using a quantitative PCR assay and immunohistochemistry with anti-XMRV specific antiserum. They found XMRV DNA and XRMV protein expression in 6% and 23% of prostate cancers and in 2% and 6% benign controls. XMRV proteins were expressed primarily in malignant epithelial cells, suggesting that retroviral infection may be directly linked to tumorigenesis. XMRV infection was associated with prostate cancer, especially higher-grade cancers.
| Comment | | |
Extensive research is being done to fight against the prostate cancer in almost all areas including prevention, screening, early diagnostic, and therapeutic strategies (surgical/radiation/medical therapy). As of now, only later two have clear roles in decreasing the mortality and morbidity from cancer but have their limitations and inherent morbidity. In contrast, former two have the maximum potential in reducing the cancer related morbidity and mortality. Current prostate cancer screening algorithms have not been found to effectively reduce the mortality. [1],[2] Except for 5-alpha reductase inhibitors, other preventive strategies (by antioxidants/vitamins) have been found useless. [3] Newer prostate cancer-specific biomolecular markers/urinary markers, gene expression signatures, and genetic changes are being defined but without any universal clinical utility or definite promise of reducing the mortality.
Xenotropic murine leukemia virus-related virus (XMRV) is the first gamma-retrovirus known to infect humans. Although gamma-retroviruses have well-characterized monogenic effects (leukemia and sarcoma) in animals, they have not been shown to cause human cancers. Authors provided experimental evidence that XMRV is indeed a gamma-retrovirus with protein composition similar to Moloney murine leukemia virus (MoMLV), another gamma-retrovirus. XRMV has been earlier detected in prostate cancer cells. [4],[5],[6],[7] However, in study by Urisman et al[4] , only the prostate cancer tissues were examined (without controls), XMRV proteins were detected in nonmalignant stromal cells, and susceptibility to XRMV infection was found in men with a specific RANSEL gene mutation. In present study, the BPH tissue as control (from TURP) was taken. XMRV proteins were detected in malignant epithelial cells implicating the possibility of one or more of the three classical mechanisms of cell transformation by retroviruses, which are (1) transduction by an oncogene, (2) transactivation of cellular growth promoting genes by retroviral gene and (3) insertional activation of a cellular oncogene, a mechanism followed by most of the leukemia-causing murine gamma-retroviruses. In an earlier study the finding of XMRV proteins only in nonmalignant stromal cells had discouraged the causal role of XMRV, because to explain the oncogenesis in that case, the new mechanisms of retroviral oncogenesis would need to be invoked. Further, the finding of independence of XMRV infection to RNASEL gene polymorphism in the present study increases the population at risk for XMRV infection from only those homozygous for the RNASEL variant to all individuals. Explanations for detection of XMRV in 6% controls (BPH tissue) in this study by Singh et al. could either be a long induction period or missed cancer in an unsampled area of the prostate. For the absence of virus proteins in many malignant cells, two possible explanations given were (1) cells without XMRV proteins never got infected with virus - a possibility that is incompatible with the known mechanism of insertional activation by murine gamma-retroviruses. (2) XMRV-infected cells lose large portions of their proviral DNA over time.
There are certain important issues related to this new finding: First, the causal role is yet to be established as it is not known whether this virus causes cancer in humans. Second, it is to be defined - at what stage or in which pathway of carcinogenesis the virus plays the role? In present study, the virus was associated with more aggressive tumors. Multiple pathways and steps in carcinogenesis are well known in certain cancers like colon cancer and are getting defined in urinary bladder cancer. Third, the mode of transmission of virus is not known - this might have important implications for prevention.
These studies are preliminary to conclude anything substantial at this stage and more studies are required to determine whether XMRV plays a causal role or whether the presence of virus is merely a function of its preferential replication in cancer cells. If causal role is confirmed, the prostate cancer research will enter into a challenging era of newer diagnostic tests, therapeutics (antiviral therapy) and vaccines, similar to cervical cancer and HPV. And this could be the ultimate right direction for dealing with this most prevalent urological cancer.
| References | | |
| 1. | Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-9.  |
| 2. | Schroder FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-8. |
| 3. | Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial. JAMA 2009;301:39-51. |
| 4. | Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, Klein EA, et al. Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog 2006;2:e25. |
| 5. | Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, et al. Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer. J Clin Virol 2008;43:277-83. |
| 6. | Dong B, Kim S, Hong S, Das Gupta J, Malathi K, Klein EA, et al. An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors. Proc Natl Acad Sci USA 2007;104:1655-60. |
| 7. | Kim S, Kim N, Dong B, Boren D, Lee SA, Das Gupta J, et al. Integration site preference of xenotropic murine leukemia virus-related virus: A new human retrovirus associated with prostate cancer. J Virol 2008;82:9964-77. |
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