Castration resistant prostate cancer: The activity of non chemotherapeutic agents

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Introduction: Androgen deprivation is a milestone for the treatment of advanced prostate cancer. Progressive disease after androgen deprivation is called "castration resistant prostate cancer" (CRPC), but the proliferation of prostate cancer remains largely mediated by androgen-receptor responsive pathways. Inhibition of the androgendependent pathways provides a new important approach for the treatment of CRPC, in addition to new drugs with a different mechanism of action. Novel approaches for castration resistant prostate cancer include: Hormonotherapies: Ketoconazole, an antifungal drug, inhibitor of multiple adrenal enzymes, whose clinical use in practice is complicated by several factors; Abiraterone acetate, a selective inhibitor of CYP450c17, adrenal enzyme which mediates androstenedione production from DHEA and 17OH progesterone; MDV3100, an androgen receptor nuclear translocation inihibitor, currently in phase III studies for chemonaïve and post docetaxel progressive CRPC; Immunotherapy: Ipilimumab, a human monoclonal antibody that overcomes CTLA-4-mediated T-cell suppression to enhance the immune response against tumor; Sipuleucel - T, a poxvirus-based vaccine targeting prostate-specific antigen (PSA), with a demonstrated improved survival in a randomized phase II trial of patients with metastatic CRPC; GVAX, an immunotherapy for prostate cancer composed of two prostate tumor cell lines modified to secrete GM-CSF, at the moment looking like an almost failing drug for CRPC; PROSTVAC-VF, an immunotherapy using genomas of two viral vectors modified in order to contain the code for PSA, ongoing in phase II clinical trials; Small molecules: Denosumab, a new bone-protective agent inhibiting RANK-L, useful for preventing scheletal-related events in patients with bone-metastatic CRPC; Sunitinib, a multikinase inhibitor that targets several growth factors receptors (VEGFR 1-2, PDGFR, Kit and RET); Everolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), the interference with mTOR pathways is associated with HIF-1 levels reduction and interaction with PI3K-AKT pathways. Conclusion: Basing on the new acknowledges reached in the past few years about the biology of prostate cancer, we dispose now of many new drugs of clinical interest for the treatment of CRPC. The most important acknowledge is that androgen related axis remains active even in the androgen-block progression phase of disease. The treatment approach of CRPC should be necessary tailored to the patients and disease characteristics.

Original languageEnglish
Title of host publicationAdenocarcinoma: Pathogenesis, Treatment And Prognosis
PublisherNova Science Publishers, Inc.
Number of pages18
ISBN (Print)9781619421738
Publication statusPublished - 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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