Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach.
The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.
Koutsilieris
Michael
M
University of Athens, Department of Basic Sciences, Medical School, 75 Micras Asias, Goudi-Athens 11527, Greece. mkouts@medscape.com
Bogdanos
John
J
Milathianakis
Constantine
C
Dimopoulos
Peter
P
Dimopoulos
Theodoros
T
Karamanolakis
Dimitrios
D
Halapas
Antonis
A
Tenta
Roxane
R
Katopodis
Haralampos
H
Papageorgiou
Effie
E
Pitulis
Nea
N
Pissimissis
Nikos
N
Lembessis
Peter
P
Sourla
Antigone
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D009919:Orchiectomy; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D019899:Paracrine Communication; D010456:Peptides, Cyclic / Q000008:administration & dosage; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D016879:Salvage Therapy; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016019:Survival Analysis; D017329:Triptorelin Pamoate / Q000008:administration & dosage
D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D006133:Growth Substances; D009363:Neoplasm Proteins; D010456:Peptides, Cyclic; D011944:Receptors, Androgen; D017329:Triptorelin Pamoate; C060347:lanreotide; D007987:Gonadotropin-Releasing Hormone; D004961:Estramustine; D013004:Somatostatin; D005047:Etoposide; D003907:Dexamethasone; D016729:Leuprolide