Phenoxodiol: isoflavone analog with antineoplastic activity.
Phenoxodiol, a synthetic analog of the plant isoflavone genistein, represents a new generation of oncology drugs acting as multiple signal transduction regulators. Phenoxodiol exerts its effect mainly by the induction of apoptosis through multiple mechanisms resulting in degradation of antiapoptotic proteins, with increased levels being linked to chemoresistance in tumor cells. Preclinical studies with this agent showed promising anticancer activity leading to a potential role in the treatment of a wide range of solid and hematologic cancers. Early clinical studies, especially in chemotherapy-resistant ovarian cancer, showed minimal toxicity with minor antitumor activity. Hormone-refractory prostate cancer is another promising area in which phenoxodiol is being actively tested. Studies are ongoing to define the optimal use of this novel anticancer agent.
Choueiri
Toni K
TK
Department of Hematology and Medical Oncology, Taussig Cancer Center, The Cleveland Clinic Foundation, 9500 Euclid Avenue, R-35, Cleveland, OH 44195, USA. choueit@ccf.org
Wesolowski
Robert
R
Mekhail
Tarek M
TM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C493956:CDKN1A protein, human; C506386:CFLAR protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones; D008246:Lysophospholipids; D059005:Topoisomerase II Inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein; C060506:sphingosine 1-phosphate; C471183:phenoxodiol; D020169:Caspases; D013110:Sphingosine