title: Investigational serine/threonine kinase inhibitors against prostate cancer metastases.
abstract: Androgen deprivation therapy (ADT) is used as first therapeutic approach in prostate cancer (PCa) although castration resistant disease (CRPC) develops with high frequency. CRPC is the consequence of lack of apoptotic responses to ADT. Alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy were used in CRPC. Serine/threonine protein kinases (STKs) regulate different molecular pathways of normal and neoplastic cells and participate to development of CRPC as well as to the progression towards a bone metastatic disease (mCRPC). Areas covered: The present review provide data on STK expression and activity in the development of CRPC as well as summarize recent reports of different strategies to block STK activity for the control of PCa progression. Expert Opinion: Inhibitors for different STKs have been developed but clinical trials in PCa are comparatively rare and few exhibit satisfactory 'drug-like' properties. It is, however, necessary to intensify, when possible, the number of clinical trials with these drugs in order to insert new therapies or combinations with standard hormone- and chemo-therapies in the treatment guidelines of the mPCA.
authors.affiliation: a Department of Biotechnological and Applied Clinical Sciences , University of L'Aquila , L'Aquila , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases
keywords: EMT; Prostate cancer; bone metastases; serine threonine kinase