420 Androgens action on prostate, biosynthesis, intratumoral synthesis, 77 metabolic pathways, androgen receptor, aromatase

Transcription

1 A Abiraterone acetate, ABT-627. See Atrasentan Active cellular immunotherapy. See Sipuleucel-T vaccine, CRPC Acute myelogenous leukemia (AML), mitoxantrone, ADAM. See Androgen deficiency of aging male Adrenal androgen synthesis inhibitor therapies abiraterone acetate, adrenalectomy, 93 aminoglutethimide, anti-androgens and anti-androgen-withdrawal, corticosteroids, CYP17 inhibitors, 98 estrogens, ketoconazole, orchiectomy and GnRH/LHRH analogs, 92 progestins, 99 progressive disease mechanisms, 93 role of androgens, 92 Adrenalectomy, 76, 93 Agonists, LHRH-I principles of oncological and gynecological use, 29 prostate cancer therapy, 34 sustained delivery systems, 29 Akt pathways, Alpha reductase androgenic steroids, 83 androgen metabolic pathway, androgens and androgen receptor, 84 antiandrogens, 83 and cancer, 85 clinical studies finasteride treatment, 86 prostate cancer prevention trial (PCPT) study, serenoa repens, 86 inhibitors, role in non-malignant disease, testosterone to dihydrotestosterone conversion, 84 Aminoglutethimide, Androgen deficiency of aging male (ADAM), 56 Androgen deprivation therapy (ADT), 273, 307 Androgen receptor antagonists BMS , 78 clinical applications antagonist withdrawal responses, 76 combined castration and AR antagonist therapy, 76 in CRPC, monotherapy in previously untreated patients, MDV3100, 78 mechanisms of action AR activation by agonist binding, role of transcriptional corepressors, structural changes, antagonist binding, monotherapy, reactivation and resistance mechanism expression of antagonist activated mutant ARs, 77 increased AR expression, 77 increased intratumoral androgen synthesis, 77 kinase signaling pathways, 78 transcriptional coactivator vs. corepressor proteins, steroidal and nonsteroidal, Androgen receptors (AR) 5 alpha reductase, 84 androgen synthesis, inhibitors, 5 antagonists, 5 (see also Androgen receptor antagonists) biology coregulators, gene amplification, 63 ligand availability, 65 mutations, posttranslational modification, role, 61 structure, castration-resistant disease, 3 chaperone inhibitors, 5 6 genes and polymorphisms, intracrine de novo synthesis of testosterone, 4 mechanism of action AR-associated coregulators, 43 dihydrotestosterone (DHT), 42 gene expression regulation, reactivation, 2 structure and function DNA-binding domain (DBD), 44 ligand-binding domain (LBD), 44 N-terminal domain (NTD), synthesis and metabolites, 42 therapeutic potential, signaling pathways,

2 420 Androgens action on prostate, biosynthesis, intratumoral synthesis, 77 metabolic pathways, androgen receptor, aromatase (CYP19A1), 114 biosynthesis and metabolism, 109, 110 cytochrome P450 17, 114 dihydrotestosterone, 109 finasteride and dutasteride effects, 116 gene fusions, 116 HSD17 gene, 115 3b-hydroxysteroid dehydrogenase, organic anion transporter OATP1B3, pharmacogenetics, prevention, 111 steroid 5a-reductase, treatment, and prostate cancer, testosterone replacement therapy follow up for prostate cancer, risk of prostate cancer, Andropause, 56 Angiogenesis, antiangiogenic agents in, 226 bevacizumab, targeting of, 209 bfgf, 200 classification of direct inhibitors of, 201 exclusive/inclusive, 202 indirect inhibitors of, combination therapies, 202 endogenous inhibitors of, 199 HIF in, and invasiveness, antineoplastic activity, 290 investigational inhibitors cytokines, 229 5,6-dimethylxanthenone acetic acid (DMXAA), 229 integrins, 229 tyrosine kinases, VEGF and VEGF-receptor (VEGF-R) family, MVD and VEGF, pharmacogenetics of antiangiogenic therapy, 234, 235 bevacizumab and thalidomide, 233 endostatin gene, HIF-1a gene, 238 metalloproteinase-1 (MMP1) gene, 240 PDGF and PDGFR gene, tumor necrosis factor (TNF) gene, 240 VEGF gene, VEGFR2, 234 rationale for, 201 resistance to, role of, surrogate markers of, 202 switch and regulatory proteins endothelial cells (ECs) in, 198 proangiogenic factors, 198 VEGF, regulation of, Antagonistic analogs, LHRH-I clinical applications, clinical findings, 31 cytotoxic analogs, in prostate cancer, degarelix, 30 development, 30 direct effects on tumors, 32 edematogenic effect, 30 gynecological and oncological use, effects on pituitary receptors, mechanism of action, 32 receptors, 32 side effects, 36 targeted cytotoxic, 33 use in BPH, 33 use in prostate cancer, Anti-angiogenesis agents, Anti-CTLA-4 immunotherapy, prostate cancer, 308, 340. See also Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade Antineoplastic activity, vitamin D angiogenesis and invasiveness, 290 apoptosis, 290 proliferation, signaling, spectrum of activity, 289 APC8015. See Sipuleucel-T vaccine, CRPC Apoptosis antineoplastic activity, 290 bcl-2 gene, 6, 8 CLU, 8 9 endothelin-1 (ET-1), 279 extrinsic and instrinsic pathways, 6 Fas-induced death, 6 Hsp27, 9 AR. See Androgen receptors Aromatase enzyme, 114 Atrasentan phase III trials in disease progression time in, 283 M00-211, M00-244, Southwestern Oncology Group (SWOG), 284 phase II trials in M96-500, M96-594, 282 B Basic fibroblast growth factor (bfgf), 200 Bcl-2 gene, 6, 8 Benign prostatic hyperplasia (BPH), 33 Bevacizumab, 227 angiogenesis pathway targeting, 209 clinical role of castrate resistant prostate cancer, castrate sensitive prostate cancer, preclinical data, success of, 210 VEGF angiogenesis regulation, targeted inhibition, 209

3 Bicalutamide, 72 Biomarkers biochemical markers, blood-based, cancer, circulating tumor cells, 395 prostate specific antigen, tissue-based, Bisphosphonates, bone metastases in androgen sensitive prostate cancer, 270 in castration-resistant prostate cancer randomized controlled trials, 269 skeletal-related events, 270 zoledronic acid, 269 denosumab, osteoporosis and fractures prevention, ADT, 273 prevention of, safety osteonecrosis of jaw (ONJ), 272 renal toxicity, 271 Blood-based protein biomarkers bone markers, 410 prostate specific antigen (PSA), protein identiifcation and quantification, protein/peptide separation, proteomic technologies, 411 sample preparation, 411 subproteomes, 411 Bone biology of anatomy, 246 cathepsin K and acid secretion, 247 components in, 246 domains, 247 OPG, RANKL, 248 genes, 289 osteoblastic metastases, osteoclastic metastases interleukin-6 (IL-6), 250 matrix metalloproteinases (MMPs), 249 PTHrP protein, RANKL and OPG, 248 osteogenic factors, 248 physiology, 267 prostate carcinoma cells and, 251 remodeling, 247 Bone metastases clinical manifestations of, 268 hypercalcemia and anemia, 256 pain, 256 c-met, endothelin axis and osteoblasts, 280 vicious cycle hypothesis, 280 endothelins (ETs), 14 osteoblastic, pathophysiology of, targeted therapies, Bortezomib, 141 Brachytherapy, C Cabazitaxel, 190 Calcitriol combination therapy, and vitamin D analogs antineoplastic agents, phase II studies, phase I studies, Cancer biomarkers classification of, 408 predictive, 408 Carboplatin, , 294 Caspase-8, 6 Castrate sensitive prostate cancer, Castration-AR antagonist therapy, 76 Castration-resistant prostate cancer (CPRC) adrenal androgen synthesis inhibitor therapies, (see also Adrenal androgen synthesis inhibitor therapies) androgen receptor antagonists in, gene amplification, 63 mutations, posttranslational modification of, signaling axis, transactivation, 7 bevacizumab CALGB treatment schema, 212 clinical trials of, 211 combinational studies, 211 clinical endpoint circulating tumor cells, 395 phase III trials, PSA based end-points, combination chemotherapy, CTLA-4 blockade, definition, 186 docetaxel, 186, endothelin receptors (see Endothelin-1 receptors, CRPC) epothilones in ixabepilone, patupilone, 187, 189, 190 phase I clinical trials of, phase II clinical trials of, pre-clinical data, 187 GVAX, and IGFBPs, 11 ligand availability, 65 mitoxantrone, 129, 402 molecular mechanisms, 3 natural history, 322 ONY-P1, 314 platinum agents (see Platinum agents) poxviral vaccine, PSA-TRICOM, sequential chemotherapy, 308 sipuleucel-t, clinical efficacy, Kaplan Meier survival benefit, 325 PA2024, recombinant prostate antigen protein, safety and tolerability,

4 422 Cathepsin K, 247 Cediranib, 228 Celecoxib trial, Cell biology androgen deprivation therapy (ADT), 2 androgen receptor (AR) androgen synthesis, inhibitors, 5 antagonists, 5 chaperone inhibitors, 5 6 intracrine de novo synthesis of testosterone, 4 reactivation, 2 transcriptional genomic action, 2 angiogenesis, apoptotic regulation bcl-2 gene, 6, 8 CLU, 8 9 extrinsic and instrinsic pathways, 6 Fas-induced death, 6 Hsp27, 9 bone metastases c-met, endothelins (ETs), 14 osteoclastic bone resorption, 14 Src inhibitors, 15 bone-predominant metastatic progression, 2 cell proliferation and survival, 1 inflammation associated proteins, 13 hedgehog pathway, 14 nuclear transcription factor (NFkB), 13 stroma-derived factor (SDF-1/CXCL12), molecular mechanisms, 3 signal transduction pathways IGF and IGF-1R, 9 11 IGFBPs and CRPC, 11 PI3K-mediated survival signaling, 12 Cetrorelix, 30, 31 Chemoprevention strategy active surveillance cohort, 356 celecoxib trial, clinical trials, elevated PSA, negative biopsy cohort, 356 exisulind effect, 356 high-grade prostatic intraepithelial neoplasia (HGPIN) cohort, 355 a(alpha)-hydroxyvitamin D2 trial, 357 PCPT, positive family history cohort, 356 pre-prostatectomy cohort, 356 REDUCE, SELECT, 360 Chromogranin A (CgA), 154 Circulating tumor cells (CTC), biomarker, 395 Cisplatin, Clusterin isoform 2 (sclu-2), 8 9 c-met, Colchicine class, Combination chemotherapy, Combined androgen blockade (CAB), 76 Combretastatin A-4, 182 Congestive heart failure (CHF), mitoxantrone, 127 Corticosteroids, Cyclooxygenase-2, inflammation, 381 Cytochrome P (CYP17), 114 abiraterone acetate, TAK-700 and TOK-001, 98 Cytochrome P450 19A1 (CYP19A1) gene, 114 Cytokines, 229 Cytotoxic drugs, Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade clinical evaluation, 344 combination therapy GM-CSF, 345 ipilimumab, 345 radiotherapy, preclinical models, regulatory T cells (Tregs), 347 T cell activation, mechanism, 344 toxicity, 346 vaccination, 347 D Degarelix, 30, 35 Denosumab, DHT. See Dihydrotestosterone Dietary risk factors biological mechanisms, meat and poultry, cruciferous vegetables, 365 fish and marine omega-3 fatty acids, 369 fruits, 365 incidence, legumes, 365 lycopene, meat, poultry, and fat, 367 milk, dairy, & calcium, 367 poultry, 368 red and processed meat, selenium, soy, 365 tomatoes, vegetables, 365 vitamin E, 366 WCRF-AICR report, 364 Diethylstilbestrol (DES), Dihydrotestosterone (DHT) action on prostate, biosynthesis, homeostasis, 54 metabolic pathways, 54, 55 structure of, 72 Dihydroxyanthracenedione (DHAD). See Mitoxantrone DNA-binding domain (DBD), 44 Docetaxel, 186, , clinical endpoints, 403 clinical implications, SWOG and TAX 327, 137 CYP3A enzymes, 164 distribution of, 164 FDA approval, mechanism of action, metabolic and transport pathway, 165 optimal timing of chemotherapy, pharmacogenetics

5 423 ABCB1, 167 ABCG2 and SLCO1B3, 167 CYP3A4 and CYP3A5, CYP1B1, 168 prostate cancer, 321 and prostatectomy, 142 prostate-specific antigen (PSA) screening, 133 and radiation therapy, SWOG docetaxel-estramustine (DE) vs. mitoxantrone-prednisone (MP), quality of life and pain scores, 137 TAX 327, taxane-based therapy, taxane-combination therapy anti-angiogenesis agents, bone targeted therapies, calcitriol combination therapy, vaccine-taxane therapy, 141 variability, non-genetic sources of age, 166 alpha1-acid glycoprotein (AAG), clearance, inter-individual variation, 164 Dolastatin peptides, 183 Drug development clinical endpoint biomarkers, phase III setting, phase II setting, FDA approved treatments approval process, challenges, cytotoxic agents, hormonal agents, 401 supportive agents, 401 Drug interactions, mitoxantrone, 126 Dutasteride, 85 87, 111 E Electrospray ionization (ESI), 412 Endogenous inhibitors, angiogenesis, 199 Endostatin, genetic variants, Endothelin-1 (ET-1) amino acid structure of, 278 axis and bone metastases, 280 and pain, effects of, plasma levels, 278 Endothelin-1 receptors, CRPC atrasentan (ABT-627) phase III trials in, phase II trials in, phase I trials, 281 EDNRB hypermethylation, 279 expression, 279 Epothilones, CRPC phase I clinical trials of ixabepilone, patupilone, 187 phase II clinical trials of combination studies, ixabepilone, patupilone, 189, 190 toxicity and, 189 pre-clinical data, 187 Estramustine, 130, 157, 402 mechanism of action, oral bioavailability of, 170 pharmacodynamic determininants, 170 pharmacogenetics, variability, non-genetic sources of, 170 Estrogens, Everolimus, 148 F Fatty-acid-CoA ligase 3 (FACL3), 290 Finasteride, 86 87, 111, Flutamide, Food and Drug Administration (FDA), drug approval challenges in, cytotoxic agents docetaxel, estramustine, 402 mitoxantrone, 402 efficacy and safety hormonal agents, 401 process, supportive agents, 401 G Gene fusions, 116 GM-CSF genes transduced vaccines (GVAX) anti-ctla-4 antibody, 340 clinical development allogeneic cells lines, 333 oligoclonal antibodies, 333 T-cell responses, transduction, 332 clinical trials Phase II-G-9803 and G-0010, Vital-1, 313, Vital-2, 314, contents, 312 phase I trial, 313 preclinical developments immunogens, irradiation, recombinant cytokines, 331 tumor antigen presentation, 331 vaccination, 331 tumor tolerance antineoplastic immune response, 338 B7-H3, 338 CTLA-4, 338 indoleamine 2,3 dioxygenase (INDO) expression, LAG-3, 338 programmed death 1 (PD1) ligation, regulatory T-cells (T-regs), 338 two dose-escalation studies, 313

6 424 Gonadotropin releasing hormone (GnRH). See Luteinizing hormone-releasing hormone-i Granulocyte stimulating factor (GM-CSF), 219 GVAX. See GM-CSF genes transduced vaccines H Heat shock protein 27 (Hsp27), 9 Hedgehog pathways, 14 Hepatic impairment, mitoxantrone, 128 Histone deacetylase inhibitors romidepsin, 150 vorinostat, 150 Hormonal drug development, 401 Hormonal therapy, platinum agents, 154 Hsp90 pathway, b-Hydroxysteroid dehydrogenase enzyme, b-Hydroxysteroid dehydrogenase (HSD17) gene, 115 Hypogonadism, 57 Hypoxia-inducible factor-1alpha (HIF-1alpha), genetic variants of, 238 I IGF. See Insulin-like growth factor Immunohistochemistry (IHC), 408 Immunomodulators (IMiDs), 139 Immunotherapy androgen-deprivation therapy, 307 anti-ctla-4, 308 antigen presentation enhancement, 306 combination chemotherapy, CTLA-4 blockade clinical evaluation, 344 combination therapy, preclinical models, regulatory T cells (Tregs), 347 T cell activation, mechanism, 344 toxicity, 346 vaccination, 347 docetaxel, 321 GM-CSF genes transduced vaccines, GVAX anti-ctla-4 antibody, 340 clinical development, clinical trials, preclinical developments, tumor tolerance, radiation therapy, 307 sequential chemotherapy, 308 sipuleucel-t clinical efficacy, Kaplan Meier survival benefit, 325 PA2024, recombinant prostate antigen protein, safety and tolerability, tumor-associated antigens, 306 vaccines antigen-presenting cell vaccines, clinical evaluation, modalities, 306 PSA-TRICOM, regulatory T-cell depletion, 314 vector-based vaccines, whole tumor-cell vaccines, Inflammation causes dietary factors, 377 hormones, 376 infectious agents, 376 prostatic and urinary factors, 377 chronic inflammation cyclooxygenase-2, 381 cytokines and growth factors, 379, 380 focal prostatic atrophy, metastasis, 382 oxidative stress, genes interleukins, macrophage scavenger receptor (MSR1), 378 prostate derived factor (PDF), 378 RNASEL, toll-like receptors (TLRs), 379 management, prostate cancer, Insulin growth factor-binding proteins (IGFBPs), 11 Insulin-like growth factor (IGF) gene expression, ligands, 9 10 pathway, 149 rational therapeutic targeting of, 10 Integrins, 229 Interleukin-6 (IL-6), 250 Isoenzyme, 84 Ixabepilone, K Kallikrein 2 (KLK2) gene, 116 Kaplan Meier survival benefit curve, CRPC, 325 Ketoconazole, L Late-onset hypogonadism (LOH), 56 Left ventricular ejection fraction (LVEF), 127 Lenalidomide in combination therapy, 221 as single agent, Leuprolide, 401 LHRH-I. See Luteinizing hormone-releasing hormone-i Ligand-binding domain (LBD), 44 Live vaccines, 127 Luteinizing hormone-releasing hormone-i (LHRH-I) agonists principles, oncological and gynecological use, 29 prostate cancer therapy, 34 sustained delivery systems, 29 amino acid sequence of, 27 antagonistic analogs clinical applications, clinical findings, 31 cytotoxic analogs, in prostate cancer, development, 30 direct effects on tumors, 32 edematogenic effect, 30 gynecological and oncological use, effects on pituitary receptors, mechanism of action, 32

7 425 receptors for LHRH type I on tumors, 32 side effects, 36 targeted cytotoxic, 33 use in benign prostatic hyperplasia (BPH), 33 use in prostate cancer, role, 27 M Mammalian target of rapamycin (mtor) inhibition, 148 Mass spectrometry (MS), Matrix-assisted laser desorption ionization (MALDI), 412 Matrix metalloproteinases (MMPs), 249 Metalloproteinase-1 (MMP1), Methoxyestradiol (2-ME), 182 Methylseleninic acid (MSA), 111 Microtubule targeting agents castrate resistant prostate cancer definition, 186 docetaxel, 186 epothilones in, cytoskeleton of dynamic instability, 180 microtubule-associated proteins (MAPs), 180 polymerization, 180 protofilaments, 180 depolymerizing agents colchicine class, combretastatin A-4, 182 definition of, 180 dolastatin peptides, methoxyestradiol (2-ME), 182 mivobulin isethionate, 182 peptides and depsipeptides, 183 vinca alkaloids, 181 drug sensitivity in cells lines selection, 185 dynamics, 186 intrinsic sensitivity, 185 non-taxane drugs, paclitaxel interaction of, 184 mechanism of, resistance to, 186 XRP6258, 190 Microvessel density (MVD) and VEGF, Mitoxantrone, 294 castration resistant prostate cancer, 402 development, 125 dosing and administration, 128 drug distribution, efficacy, 129 mechanism of action, , 168 and pharmacodynamic determininants, pharmacogenetics, 169 pharmacokinetics, pharmacological considerations, 126 safety and precautions adverse reactions, 128 black-box warnings, 127 pregnancy, 128 therapy castration resistant prostate cancer (CRPC), 129 docetaxel and estramustine, 130 mitoxantrone vs.docetaxel, variability, non-genetic sources of, 169 N Neuroendocrine differentiation (NE), platinum agents androgen-independent subpopulation, 155 chromogranin A (CgA), 154 hormonal therapy, 154 in vitro and in vivo assays, LNCaP cells, 155 Nilutamide, Non-steroidal anti-inflammatory agents (NSAIDs), 291 Nonsteroidal AR antagonists, N-terminal domain (NTD), 43 44, 62, 63 Nuclear receptor coregulators androgen receptor basic mechanism, structure and function, synthesis and metabolites, 42 therapeutic potential, signaling pathways, clinical relevance and therapeutic potential in CaP AR-associated coregulators, 45, 46 coregulator expression, 45 targeting coregulator activity, targeting coregulator expression, 47 Nuclear transcription factor (NFkB), 13 O OATP1B3, organic anion transporter, 105, , 167 Office of Oncology Drug Products (OODP), 400 Omega-3 fatty acids, 369 Oncogene beta-catenin, 66 Oncologic Drugs Advisory Committee (ODAC), 400 ONY-P1, 314 Orchiectomy, 92 Osteoblastic bone metastases, , See also Bone metastases Osteoclastic bone metastases interleukin-6 (IL-6), 250 matrix metalloproteinases (MMPs), 249 PTHrP protein, RANKL and OPG, 248 Osteoclastic bone resorption, 14 Osteoclastogenesis inhibitory factor (OCIF). See Osteoprotegerin (OPG) Osteonecrosis of jaw (ONJ), 272 Osteoprotegerin (OPG), Oxaliplatin, 157 Oxidative stress, chronic inflammation, P p53, 199 Paclitaxel, 134 interaction of, 184 mechanism of, Pain, endothelin-1 (ET-1), Parathyroid hormone-related protein (PTHrP), Patupilone, 187, 189, 190

8 426 PDGF. See Platelet-derived growth factor Pharmacogenetics angiogenesis endostatin gene, HIF-1a gene, 238 metalloproteinase-1 (MMP1) gene, 240 PDGF and PDGFR gene, tumor necrosis factor (TNF) gene, 240 VEGF gene, a-reductase inhibitors, 116 docetaxel, estramustine, human CaP and LNCaP cell lines, mitoxantrone, 169 SLCO1B3 gene, 117 Pharmacology docetaxel, estramustine, 170 mitoxantrone, 169 satraplatin, 172 Phosphatase and tensin homologue (PTEN), 12 Phosphatidylinositol 3-kinase (PI3K)-signaling, 12 Picoplatin, 157 PI3 kinase/akt pathways, Pituitary LHRH receptors, Platelet-derived growth factor (PDGF), 13, Platelet-derived growth factor receptor (PDGFR) bone tropism of, 239 patient selection, PC-3MM2-MDR cells, 239 and VEGF, 239 Platinum agents cisplatin and carboplatin, first-line chemotherapy multiagent regimens, single-agent, neuroendocrine differentiation (NE) in androgen-independent subpopulation, 155 chromogranin A (CgA), 154 hormonal therapy, 154 in vitro and in vivo assays, LNCaP cells, 155 oxaliplatin, 157 picoplatin, 157 second-line therapy carboplatin, 158 satraplatin and prednisone, 158 Progestins, 99 Prostate cancer prevention trial (PCPT) adverse events, 358 finasteride evaluation, 358 steroids, 357 tumor grade assessment, Prostatectomy, 142 Prostate specific antigen (PSA) blood-based biomarker, clinical trial endpoint limitations, 394 progression, response, 393 Proteomics applications blood-based protein biomarkers, cancer biomarkers, SELDI-TOF, tissue-based protein biomarkers diagnostic, 408 prognostic, R Radiation therapy, , 291, 307 Radical prostatectomy, 57 Radiopharmaceuticals chemotherapy and doxorubicin, Sm-EDTMP and docetaxel, Sr and cisplatin, 264 comparison trials, guidelines for, indications and contraindications for, 258 physical properties and mechanisms of, radium bone-metastatic CRPC patients, 263 phase I clinical trial, 262 phase II clinical trial, 262 phase III trials, samarium-edtmp pain scores in, 261 placebo-controlled randomized trials in, 260 repetitive doses of, strontium pain in, 259 randomized trial in, repeated doses of, 260 uses of, Radium, 262 Receptor activator of NF-kB (RANK), Receptor activator of nuclear factor kappa B ligand (RANKL), 248 Reduction by Dutasteride of Prostate Cancer Events Trial (REDUCE), Renal failure, bisphosphonates, Renal impairment, mitoxantrone, 128 Retinoid receptor ligands, 291 Romidepsin, 150 S 153 Samarium-EDTMP, Satraplatin, 158 JM118, mechanism of action, 171 variability, non-genetic sources of, 172 Selective reaction monitoring (SRM), 413 Selenium and Vitamin E Cancer Prevention Trial (SELECT), 360 Selenium, dietary risk factor, Serenoa repens, 86 Signal transduction pathways IGF and IGF-1R, 9 11 IGFBPs and CRPC, 11 PI3K-mediated survival signaling, 12 Single nucleotide polymorphisms (SNPs), 235

9 Sipuleucel-T vaccine, CRPC clinical efficacy D9902A study, developmental history, 325 D9901 study, phase III clinical studies, 323, 324 phase I/II studies, 323, 324 Kaplan Meier survival benefit, 325 metastatic, nonmetastatic, 312 PA2024, recombinant prostate antigen protein, safety and tolerability, Skeletal-related event (SRE), 270 Solute carrier organic anion transporter 1B3 (SLCO1B3) gene, Somatic 5-alpha reductase mutations, 85 Sorafenib, 139, 228 Southwestern Oncology Group Intergroup protocol (SWOG 99-16) clinical implications, 137 docetaxel-estramustine (DE) vs. mitoxantrone-prednisone (MP), quality of life and pain scores, 137 SRC-1, 65 Steroid 5a-reductase (SRD5A), Steroids, AR antagonists, 71 Stroma-derived factor (SDF-1/CXCL12), Strontium, Sunitinib, 139, 228 Surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF), T TAK-700, CYP17 inhibitor, 98 Tamoxifen, 291 Tandutinib, Targeted cytotoxic analog therapy, 33 TAX 327 clinical implications, 137 discrepancies, 136 follow-up survival analysis, 136 neutropenia, pain reduction and quality of life, 135 Taxane chemotherapy, 157 combination therapy anti-angiogenesis agents, bone targeted therapies, calcitriol combination therapy, vaccine-taxane therapy, 141 cytotoxicity, 134 docetaxel with estramustine, paclitaxel, 134 Taxol. See Paclitaxel Taxotere. See Docetaxel Testosterone, 42 conversion to dihydrotestosterone, 84 deficiency, Testosterone replacement therapy (TRT) follow up for prostate cancer, risk of prostate cancer, Thalidomide analogs, 220 in combination therapy bevacizumab and prednisone, 219 cyclophosphamide, dexamethasone, 218 docetaxel, 217 estramustine, 218 granulocyte stimulating factor (GM-CSF), 219 paclitaxel, 218 trials in, lenalidomide in combination therapy, 221 as single agent, as single agent phase III study vs. placebo, 216 phase II study of, 216 trials in, 217 tumor microenvironment, 217 TIF-2 overexpression, 65 Tissue-based protein biomarkers diagnostic, 408 prognostic, TOK-001, 98 Toll-like receptors (TLRs), inflammation, 379 Transcriptional-coactivating protein, Transcriptional corepressors vs. coactivator proteins, role in AR antagonist action, TRT. See Testosterone replacement therapy Tumor necrosis factor (TNF), 240 TNF-a, 379 Tyrosine kinases AZD2171 (cediranib), 228 sorafenib, 228 sunitinib, 228 tandutinib, V Vaccines antigen-presenting cell vaccines, clinical evaluation, GM-CSF genes transduced vaccines, GVAX anti-ctla-4 antibody, 340 clinical development, clinical trials, preclinical developments, tumor tolerance, live, 127 modalities, 306 PSA-TRICOM, regulatory T-cell depletion, 314 vector-based vaccines, whole tumor-cell vaccines GVAX, ONY-P1, 314

10 428 Vaccine-taxane therapy, Vascular endothelial growth factor (VEGF), 12 13, , angiogenesis inhibitors, angiogenesis regulation, genetic variants of gene gene interaction, haplotype, 237 polymorphisms, thrombospondin-1 (TSP1), 236 targeted inhibition, 209 Vinca alkaloids, 181 Visual analog scale (VAS), Vitamin D antineoplastic activity angiogenesis and invasiveness, 290 apoptosis, 290 proliferation, signaling, spectrum of activity, 289 calcitriol and analogs, cytotoxic chemotherapy, 291 phase II studies, phase I studies, steroids, epidemiology of dairy product consumption, outcomes, 288 solar UV radiation, 287 vitamin D receptor (VDR), 288 NSAIDs, 291 radiation, 291 retinoid receptor ligands, 291 tamoxifen, 291 Vitamin D receptor (VDR), 288 Vitamin E, 366 Vorinostat, 150 W World Cancer Research Fund and American Institute for Cancer Research (WCRF AICR) report, 364 Z Zoledronic acid, 269, 401