title: Molecular profiles of finasteride effects on prostate carcinogenesis.
abstract: Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1374, Houston, Texas 77030, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Jeri
authors.initials: J
authors.lastname: Kim
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000728:Androgens / Q000502:physiology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001378:Azasteroids / Q000494:pharmacology / Q000627:therapeutic use; D013196:Dihydrotestosterone / Q000378:metabolism; D018450:Disease Progression; D000068538:Dutasteride; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D018120:Finasteride / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology / Q000517:prevention & control*; D018579:Patient Selection; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000473:pathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D001378:Azasteroids; D007527:Isoenzymes; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D018120:Finasteride; D000068538:Dutasteride