Targeted Therapies In Prostate And Renal Cancers

Main Category: Urology / Nephrology
Also Included In: Prostate / Prostate Cancer;  Cancer / Oncology
Article Date: 02 Nov 2008 - 0:00 PST

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MONTEREY, CA, USA (UroToday.com) - In this session, Christopher P. Evans presented a State-of-the-Art lecture on molecular targets in prostate and renal cancers. Molecular targets in cancer diagnosis and therapy have come to the fore of the oncology field in the last decade. Their identification is rooted in basic science investigation and enhanced knowledge in the fields of genetics, biochemistry, molecular and tumor biology, and pathology, among others. Molecular targets are often biomarkers, either prognostic ones that reflect the natural history of the cancer, or predictive ones that reflect the impact of a therapy.

Molecular targets in urologic cancer may arise from four sources; the host, the tumor, as a result of a treatment, or associated with a specific disease stage. An example of a host-specific molecular biomarker includes the 5 single nucleotide polymorphisms combined with a family history of prostate cancer that results in a 9-fold increase in risk of Swedish men developing CaP. An example of tumor specific targets includes the different gene mutations in hereditary kidney cancers. While clear cell carcinomas have VHL gene mutations, hereditary papillary type 1 kidney cancer has a gene fusion of the c-Met oncogene, and type 2 has an alteration in the fumarate hydratase enzyme in the Krebs cycle. These differences direct targeted therapies for different histologies.

Many targets arise following a specific therapy for the disease. For example, he presented data that androgen deprivation therapy for prostate cancer results in 77 identified up- or downregulated genes to include neuropeptides, signaling molecules, interleukins, and apoptotic genes among others. His lab has developed a model targeting one of these genes, the non-receptor tyrosine kinase Src. A neuropeptide overexpressing cell line that upregulates Src had a 100% metastatic rate in SCID mice, of which 100% of metastases were inhibited using the Src specific inhibitor AZD0530. As an example of stage specific targets, he showed that Src is upregulated in metastatic CaP in bone, by both the tumor cells and osteoclasts. AZD0530 inhibited both osteoclast and CaP proliferation and stabilized the tibias in mice undergoing direct PC3 prostate cancer cell injection. Both of these models have led to Phase II clinical trials using this agent.

Presented by Christopher P. Evans, MD, at the 84th Annual Meeting of the AUA - Western Section - October 26 - 30, 2008 - Monterey, California

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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