Dr. Nima Sharifi
PSA Rising /DALLAS/ – July 25, 2011 – UT Southwestern Medical Center researchers have narrowed the potential drug targets for advanced prostate cancer by demonstrating that late-stage tumors are driven by a different hormonal pathway than previously was thought.
“We have recently discovered that castration resistant prostate cancer (CRPC) is unexpectedly driven by dihydrotestosterone synthesis from adrenal precursors in a pathway that circumvents testosterone,” says Dr. Nima Sharifi, assistant professor of internal medicine and senior author of a study in Proceedings of the National Academy of Sciences.
“The dominant pathway to DHT synthesis from adrenal precursors in CRPC [castration resistant prostate cancer] follows an alternative route that bypasses T and requires steroid 5α-reductase isoenzyme-1 (SRD5A1),” Dr. Sharifi writes.
February 7 2011, BUFFALO, NY — The nation’s first FDA-approved cancer treatment vaccine, Provenge (sipuleucel-T), is being offered for the first time in Western New York at Roswell Park Cancer Institute (RPCI). The vaccine is designed for men with advanced prostate cancer who have limited treatment options and who meet eligibility requirements.
From ASCO annual general meeting, 2007, comes this abstract of a study by A. Reichle, B. Walter, A. Berand, M. Vogelhuber, K. Bross, J. Wilke, W. Wieland, R. Andreesen, S. Rogenhofer.
Background: The present multi-centre phase II study was designed to support the hypothesis that networking agents binding to ubiquitous accessible targets in metastatic hormone-refractory prostate cancer (HRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating objective response (primary endpoint).
Cougar Biotechnology’s once-daily oral drug CB7630 (abiraterone acetate), based on recently announced trial results, appears o have some efficacy at two stages of the standard treatment path for androgen independent prostate cancer — either before or after chemotherapy.
A UK Phase I/II trial of CB7630 reports positive signs among a small number of patients enrolled so far in a trial for AIPC men who have never taken chemotherapy but have taken LHRH analogues and multiple other hormonal therapies, including antiandrogens, diethylstilboestrol and dexamethasone. In addition, a Phase II trial ongoing at several US centers and in the UK indicates that CB7630 may benefit some patients who have used up Taxotere (docetaxel) chemotherapy.
CB7630 (abiraterone acetate) is reported to have “minimal toxicity” (as yet no maximum tolerated dose has been reached). Among the small numbers of patients treated so far, benefits include lowering of PSA’s, some tumor shrinkage, and some pain reduction. In one of the trials, out of “20 evaluable patients with measurable tumor lesions, treatment with CB7630 resulted in partial radiological responses (as measured
by the RECIST criteria) in 11 patients (55%), with 7 patients demonstrating ongoing stable disease and 3 patients experienced regressing bone disease.”
The company says CB7630 “has the potential to be used by both urologists who treat patients with second line hormonal therapies and by medical oncologists who treat patients in the second line chemotherapy setting…” To that end, the company chose to announce results at AACR, aiming the presentation toward oncologists, and again at AUA:
Cougar Biotechnology Announces Interim Phase II Results Confirm
Efficacy of CB7630 in Both Chemotherapy NaÃƒÂ¯ve and Chemotherapy
Refractory Prostate Cancer Patients April 17 (posted May 31) 2007.
Cougar . . . Presentation of Positive CB7630 (abiraterone acetate)
Clinical Data at AUA Annual Meeting May 21 (posted May 31), 2007
For three UK and US trials ongoing see: