UPDATE ON CASTRATE RESISTANT PROSTATE CANCER

UPDATE ON CASTRATE RESISTANT PROSTATE CANCER

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Title:	UPDATE ON CASTRATE RESISTANT PROSTATE CANCER
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Article_Title:	UPDATE ON CASTRATE RESISTANT PROSTATE CANCER
Authors:	MUREȘANU Horia, IOIART Ioan
Affiliation:	Department of Urology, Faculty of Medicine, Vest University Vasile Goldiș, Arad, Romania
Abstract:	Based on the increased understanding of the biochemical pathways that promote tumor survival a range of new treatments become available. Drug development based on biology-guided rationale coupled with intelligent trial design will find promising new treatment options for castrate resistant prostate cancer (CRPC). The androgen receptor plays the key role in prostate cancer even during castrate resistance, and therapies targeting it represent the future for treating CRPC. During progression to CRPC induced by persistent androgen deprivation, androgen receptor (AR) signaling is maintained through a variety of mechanism including increased expression of AR, amplification of the AR gene, and structural changes in AR caused by genetic mutations or mRNA splice variants. Clinical consideration has been added to the conventional staging criteria to describe the extent of the disease beyond the simple anatomic classification. For patients with metastatic CRPC who have previously received docetaxel chemotherapy Abiraterone acetate is a novel androgen biosynthesis inhibitor that has gained FDA approval. For men with asymptomatic or minimally symptomatic metastatic CRPC Sipuleucel-T is the first therapeutic vaccine to be FDA approved. Immunotherapy also has several potential benefits for patients with CRPC, including lack of toxicity and maintains of quality of life. It is an exciting time in the management of CRCP with new agents under development. Such evolution in treatment approach will necessitate an evolution of the urologist from being primary a surgeon to becoming more an applied molecular biologist.
Keywords:	Castrate resistant prostate cancer, androgen receptor, androgen receptor -independent and androgen receptor -dependent mechanism
References:	1. Isaacs JT, Coffey DS. Adaptation vs. selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 1981 Dec;41(12 Pt 1):5070-5. 2. Heidenreich A, Bastian PJ, Bellmunt J et al. Guidelines on prostate cancer 2012. Available at: hptt://www.uroweb.org/gls/pdf/08_Prostate_Cancer.pdf 3. Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008;26:1148-59 4. Cookson MS, Roth BJ, Dahm P, et al. Castration-Resistant Prostate Cancer: AUA Guideline http://www.auanet.org/education/guidelines/castration-resistant-prostate-cancer.cfm 5. Lunardi A, Ala U, Epping MT et al. A Co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 2013; 45:747-55 6. Stanevsky Y, Tsivian A, Tsivian M. Castration-resistant prostate cancer: a strategy to enhance response to androgen deprivation. Asian J Androl 2013;2:10.1038/aja.2013.96 7. Knudsen KE and Kelly WK. Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer. Expert Rev Endocrinol Metab. 2011;6(3): 483-493 8. Taplin ME, Bubley GJ, Shuster TD, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 1995 May;332(21):1393-8. 9. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001;61(9):3550–3555. 10. Chi KN, Bjartell A, Dearnaley D, et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment targets. Eur Urol. 2009 Oct;56(4):594-605. 11. Attard G, Cooper CS, de Bono JS. Steroid hormone receptors in prostate cancer: a hard habit to break? Cancer Cell 2009 Dec 8;16(6):458-62. 12. Schröder FH. Progress in understanding androgen-independent prostate cancer (AIPC): a review of potential endocrine-mediated mechanisms. Eur Urol 2008 Jun;53(6):1129-37. 13. Haldar S, Basu A, Croce CM. Bcl-2 is the guardian of microtubule integrity. Cancer Res 1997 Jan;57(2):229-33. 14. Stapleton AM, Timme TL, Gousse AE, et al. Primary human prostate cancer cells harboring p53 mutations are clonally expanded in metastases. Clin Cancer Res 1997 Aug;3(8):1389-97. 15. Bauer JJ, Sesterhenn IA, Mostofi FK, et al. Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol 1996 Oct;156(4):1511-6. 16. Theodorescu D, Broder SR, Boyd JC, et al. p53, bcl-2 and retinoblastoma proteins as long-term prognostic markers in localized carcinoma of the prostate. J Urol 1997 Jul;158(1):131-7. 17. MacGrogan D, Bookstein R. Tumor suppressor genes in prostate cancer. Semin Cancer Biol 1997 Feb;8(1):11-9. 18. Chi KN. Targeting Bcl-2 with oblimersen for patients with hormone refractory prostate cancer. World J Urol 2005 Feb;23(1):33-7. 19. Zhang Z, Li M, Wang H, Agrawal S, et al. Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci USA 2003 Sep;100(20):11636-41. 20. Verhagen PC, van Duijn PW, Hermans KG, et al. The PTEN gene in locally progressive prostate cancer is preferentially inactivated by bi-allelic gene deletion. J Pathol 2006 Apr;208(5):699-707. 21. Ruijter E, van de Kaa C, Miller G, et al. Molecular genetics and epidemiology of prostate carcinoma. Endocr Rev 1999 Feb;20(1):22-45.
Read_full_article:	pdf/vol15/iss1-4/7 JMA 2012 MuresanuH – Update on castrate prostate cancerzz.pdf
Correspondence:	Muresanu Horia Spitalul Clinic Judetean de Urgenta Arad Email: hmuresanu@gmail.com

	Read full article
Article Title:	UPDATE ON CASTRATE RESISTANT PROSTATE CANCER
Authors:	MUREȘANU Horia, IOIART Ioan
Affiliation:	Department of Urology, Faculty of Medicine, Vest University Vasile Goldiș, Arad, Romania
Abstract:	Based on the increased understanding of the biochemical pathways that promote tumor survival a range of new treatments become available. Drug development based on biology-guided rationale coupled with intelligent trial design will find promising new treatment options for castrate resistant prostate cancer (CRPC). The androgen receptor plays the key role in prostate cancer even during castrate resistance, and therapies targeting it represent the future for treating CRPC. During progression to CRPC induced by persistent androgen deprivation, androgen receptor (AR) signaling is maintained through a variety of mechanism including increased expression of AR, amplification of the AR gene, and structural changes in AR caused by genetic mutations or mRNA splice variants. Clinical consideration has been added to the conventional staging criteria to describe the extent of the disease beyond the simple anatomic classification. For patients with metastatic CRPC who have previously received docetaxel chemotherapy Abiraterone acetate is a novel androgen biosynthesis inhibitor that has gained FDA approval. For men with asymptomatic or minimally symptomatic metastatic CRPC Sipuleucel-T is the first therapeutic vaccine to be FDA approved. Immunotherapy also has several potential benefits for patients with CRPC, including lack of toxicity and maintains of quality of life. It is an exciting time in the management of CRCP with new agents under development. Such evolution in treatment approach will necessitate an evolution of the urologist from being primary a surgeon to becoming more an applied molecular biologist.
Keywords:	Castrate resistant prostate cancer, androgen receptor, androgen receptor -independent and androgen receptor -dependent mechanism
References:	1. Isaacs JT, Coffey DS. Adaptation vs. selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 1981 Dec;41(12 Pt 1):5070-5. 2. Heidenreich A, Bastian PJ, Bellmunt J et al. Guidelines on prostate cancer 2012. Available at: hptt://www.uroweb.org/gls/pdf/08_Prostate_Cancer.pdf 3. Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008;26:1148-59 4. Cookson MS, Roth BJ, Dahm P, et al. Castration-Resistant Prostate Cancer: AUA Guideline http://www.auanet.org/education/guidelines/castration-resistant-prostate-cancer.cfm 5. Lunardi A, Ala U, Epping MT et al. A Co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 2013; 45:747-55 6. Stanevsky Y, Tsivian A, Tsivian M. Castration-resistant prostate cancer: a strategy to enhance response to androgen deprivation. Asian J Androl 2013;2:10.1038/aja.2013.96 7. Knudsen KE and Kelly WK. Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer. Expert Rev Endocrinol Metab. 2011;6(3): 483-493 8. Taplin ME, Bubley GJ, Shuster TD, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 1995 May;332(21):1393-8. 9. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001;61(9):3550–3555. 10. Chi KN, Bjartell A, Dearnaley D, et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment targets. Eur Urol. 2009 Oct;56(4):594-605. 11. Attard G, Cooper CS, de Bono JS. Steroid hormone receptors in prostate cancer: a hard habit to break? Cancer Cell 2009 Dec 8;16(6):458-62. 12. Schröder FH. Progress in understanding androgen-independent prostate cancer (AIPC): a review of potential endocrine-mediated mechanisms. Eur Urol 2008 Jun;53(6):1129-37. 13. Haldar S, Basu A, Croce CM. Bcl-2 is the guardian of microtubule integrity. Cancer Res 1997 Jan;57(2):229-33. 14. Stapleton AM, Timme TL, Gousse AE, et al. Primary human prostate cancer cells harboring p53 mutations are clonally expanded in metastases. Clin Cancer Res 1997 Aug;3(8):1389-97. 15. Bauer JJ, Sesterhenn IA, Mostofi FK, et al. Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol 1996 Oct;156(4):1511-6. 16. Theodorescu D, Broder SR, Boyd JC, et al. p53, bcl-2 and retinoblastoma proteins as long-term prognostic markers in localized carcinoma of the prostate. J Urol 1997 Jul;158(1):131-7. 17. MacGrogan D, Bookstein R. Tumor suppressor genes in prostate cancer. Semin Cancer Biol 1997 Feb;8(1):11-9. 18. Chi KN. Targeting Bcl-2 with oblimersen for patients with hormone refractory prostate cancer. World J Urol 2005 Feb;23(1):33-7. 19. Zhang Z, Li M, Wang H, Agrawal S, et al. Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci USA 2003 Sep;100(20):11636-41. 20. Verhagen PC, van Duijn PW, Hermans KG, et al. The PTEN gene in locally progressive prostate cancer is preferentially inactivated by bi-allelic gene deletion. J Pathol 2006 Apr;208(5):699-707. 21. Ruijter E, van de Kaa C, Miller G, et al. Molecular genetics and epidemiology of prostate carcinoma. Endocr Rev 1999 Feb;20(1):22-45.
*Correspondence:	Muresanu Horia Spitalul Clinic Judetean de Urgenta Arad Email: hmuresanu@gmail.com

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