In April 2011, abiraterone acetate (Zytiga; Centocor Ortho Biotech), in combination with prednisone, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
"The results of studies on androgen-targeted therapies in prostate cancer should be considered as we search for optimal therapies for AR+ TNBCs. Recent studies regarding the efficacy of the FDA approved Abiraterone acetate (68-73) in castration-resistant prostate carcinoma (CRPC) has shown promising results     "
[Show abstract][Hide abstract] ABSTRACT: Background:
Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy.
400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers.
Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), while 50 tumors (12.5%) were triple negative (ER-, PR-, Her2-); 18 (36%) of the triple negative tumors were AR positive and 10 (55%) of these were classic apocrine carcinomas. Fourteen cases, all apocrine carcinomas, were AR and Her2 positive. All 32 QN carcinomas were poorly differentiated and they had the highest Ki67 labeling index.
The relatively high proportion of AR+ tumors (36%) among the 50 triple negative carcinomas is an important finding in support of routine assessment of AR in at least all TNBCs and apocrine carcinomas as a potential target for therapy.
American Journal of Cancer Research 07/2014; 4(4):353-68. · 4.17 Impact Factor
"In glucocorticoids, introduction of halogen substituents (mostly fluorine), additional double bonds, and oxygen-containing groups (alcohols, acetals) resulted in significant enhancement of activity and selectivity , whereas the annulation of additional heterocyclic rings (typically at the C-2,C-3 flank) resulted in compounds with various biological activities  . Azasteroids containing protonable nitrogen atoms at various positions of the steroid backbone or the side-chain exhibit antifungal activities, with most of them mimicking carbocationic high energy intermediates (HEI) of enzymatic steps in the postsqualene part of ergosterol biosynthesis , whereas abiretarone, containing a pyridine ring in place of the aliphatic side chain at C-17, is a potent inhibitor of the enzyme 17α- hydroxylase/C17,20-lyase used therapeutically in cancer therapy due to its androgenlowering activity . Recently, our group reported about highly cytotoxic 1,4-dioxo-5,10- diazasteroids . "
[Show abstract][Hide abstract] ABSTRACT: This paper describes a convenient approach to the 7-aza-des-A-steroid (6,6a,7,8,9,9a-hexahydro-5H-cyclopenta[h]quinoline) scaffold starting from Grundmann's ketone using two different pyridine annulation protocols. The biological evaluation of the pyridine and pyridinium products revealed that these compounds unexpectedly do not interfere with ergosterol and cholesterol biosynthesis. The pyridinium compound 6 showed significant antimicrobial and cytotoxic activities which are most likely due to its detergent-like structure.
Scientia Pharmaceutica 06/2013; 81(2):329-38. DOI:10.3797/scipharm.1303-03
"Cabazitaxel (154) (Jevtana®)  (Fig. 10), a novel taxane derivative, has been recently approved for metastatic CRPC (mCRPC), which has progressed following docetaxel therapy, whereas the immunotherapy Sipuleucel-T (Provenge ® ) has been approved for the treatment of asymptomatic or minimally symptomatic mCPRC. In April 2011, abiraterone acetate (156) (Zytiga ® ) (Fig. 10) became the first steroidal CYP17 inhibitor to be approved by the FDA for the treatment of docetaxelresistant mCRPC     . Enzalutamide (158) (Xtandi®)  an androgen receptor (AR) antagonist that prevents androgens to binding the AR and nuclear translocation and co-activator recruitment of the ligand-receptor complex has been approved by the FDA, in August of 2012, for the treatment of CRPC. "
[Show abstract][Hide abstract] ABSTRACT: The role of steroidal inhibitors of androgen biosynthesis as potential weapons in the treatment of prostatic diseases, such as benign prostatic hyperplasia and prostatic cancer will be reviewed. Two enzymes have been targeted in the development of inhibitors that potentially could be useful in the management of such conditions. 5α-Reductase is primarily of interest in benign prostatic disease, though some role in the chemoprevention of prostatic carcinoma have been considered, whereas the 17α-hydroxylase/17,20-lyase (CYP17) enzyme is of interest in the treatment of malignant disease. An overview of the main achievements obtained during the past years will be presented, however special focus will be made on steroidal molecules that reached clinical trials or have been commercially launched. Relevant examples of such drugs are finasteride, dutasteride, abiraterone acetate and galeterone (TOK-001, formerly known as VN/124-1).
The Journal of steroid biochemistry and molecular biology 05/2013; 137. DOI:10.1016/j.jsbmb.2013.04.006 · 3.63 Impact Factor
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