Abstract
Prostate cancer is the most common and second most lethal cancer in men. The majority of prostate cancers are histologically similar to acinar adenocarcinomas and rely on androgen-dependent signaling for their development and progression. Androgen deprivation therapy is a mainstay of treatment regimens and we discuss the recent advancements in androgen-deprivation therapy. Recent advances in defining the genetic landscape of prostate cancer have shown that the depth of genetic heterogeneity surpasses what can be seen histologically and has the ability to redefine treatments. TMPRSS2–ETS family fusion proteins are unique to prostate cancer and we discuss their role in carcinogenesis, prognosis, and the development of TMPRSS2–ETS family gene fusion targeted therapy. Inactivation of the tumor suppressor PTEN leads to activation of the PI3K/Akt/mTOR pathway and we discuss the prognostic and treatment implications. Molecular genetic analysis has recently demonstrated that clinically aggressive high grade neuroendocrine prostate carcinomas contain a high prevalence of overexpression of Aurora A kinase and N-myc. We discuss the role of Aurora A kinase and N-myc in the development of the aggressive neuroendocrine phenotype and the development of targeted inhibitors of this specific genetic subtype. Lastly, we briefly discuss emerging genetic subtypes defined by either SPINK1 overexpression, CHD1 inactivation, or SPOP mutations. By reviewing the associations between the morphologic features and the molecular genetics of prostate cancer we hope to provide insight and guidance to the emerging options for targeted therapy.
Keywords: Androgen receptor, molecular cytogenetics, neuroendocrine/small cell carcinoma, personalized medicine, prostate, targeted therapy, TMPRSS2-ERG rearrangement.
Current Drug Targets
Title:Molecular Foundations for Personalized Therapy in Prostate Cancer
Volume: 16 Issue: 2
Author(s): Kurt W. Fisher, Rodolfo Montironi, Antonio Lopez Beltran, Holger Moch, Lisha Wang, Marina Scarpelli, Sean R. Williamson, Michael O. Koch and Liang Cheng
Affiliation:
Keywords: Androgen receptor, molecular cytogenetics, neuroendocrine/small cell carcinoma, personalized medicine, prostate, targeted therapy, TMPRSS2-ERG rearrangement.
Abstract: Prostate cancer is the most common and second most lethal cancer in men. The majority of prostate cancers are histologically similar to acinar adenocarcinomas and rely on androgen-dependent signaling for their development and progression. Androgen deprivation therapy is a mainstay of treatment regimens and we discuss the recent advancements in androgen-deprivation therapy. Recent advances in defining the genetic landscape of prostate cancer have shown that the depth of genetic heterogeneity surpasses what can be seen histologically and has the ability to redefine treatments. TMPRSS2–ETS family fusion proteins are unique to prostate cancer and we discuss their role in carcinogenesis, prognosis, and the development of TMPRSS2–ETS family gene fusion targeted therapy. Inactivation of the tumor suppressor PTEN leads to activation of the PI3K/Akt/mTOR pathway and we discuss the prognostic and treatment implications. Molecular genetic analysis has recently demonstrated that clinically aggressive high grade neuroendocrine prostate carcinomas contain a high prevalence of overexpression of Aurora A kinase and N-myc. We discuss the role of Aurora A kinase and N-myc in the development of the aggressive neuroendocrine phenotype and the development of targeted inhibitors of this specific genetic subtype. Lastly, we briefly discuss emerging genetic subtypes defined by either SPINK1 overexpression, CHD1 inactivation, or SPOP mutations. By reviewing the associations between the morphologic features and the molecular genetics of prostate cancer we hope to provide insight and guidance to the emerging options for targeted therapy.
Export Options
About this article
Cite this article as:
W. Fisher Kurt, Montironi Rodolfo, Beltran Lopez Antonio, Moch Holger, Wang Lisha, Scarpelli Marina, Williamson R. Sean, Koch O. Michael and Cheng Liang, Molecular Foundations for Personalized Therapy in Prostate Cancer, Current Drug Targets 2015; 16 (2) . https://dx.doi.org/10.2174/1389450115666141229154500
DOI https://dx.doi.org/10.2174/1389450115666141229154500 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response, and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Meet Our Editorial Board Member
Mini-Reviews in Medicinal Chemistry Human Defensins: Synthesis and Structural Properties
Current Pharmaceutical Design Prophylaxis of Erectile Function After Radical Prostatectomy with Phosphodiesterase Type 5 Inhibitors
Current Pharmaceutical Design Soy Saponins and the Anticancer Effects of Soybeans and Soy-Based Foods
Current Medicinal Chemistry - Anti-Cancer Agents Micro-/Nano-Scale Biointerfaces, Mechanical Coupling and Cancer Therapy
Current Topics in Medicinal Chemistry Tumor Specific Novel Taxoid-Monoclonal Antibody Conjugates
Current Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Exploration of the Mechanism of Kaempferol in the Treatment of Cervical Cancer-based on Metabolomics and Network Pharmacology
Current Pharmaceutical Design Biomarkers for Colorectal Cancer: Identification Through Proteomics
Current Proteomics Design, Synthesis, Characterisation, and Evaluation of Substituted Quinolin-2-one Derivatives as Possible Anti-lung Cancer Agents
Current Drug Discovery Technologies Prostate Cancer Prevention in the Developing World - What are we Waiting for?
Current Pharmacogenomics and Personalized Medicine Estrogen Receptor Signaling: Impact on Cell Functions
Current Signal Transduction Therapy Identification of Small Molecule Sulfonic Acids as Ecto-5'-Nucleotidase Inhibitors
Medicinal Chemistry BPS and BPF are as Carcinogenic as BPA and are Not Viable Alternatives for its Replacement
Endocrine, Metabolic & Immune Disorders - Drug Targets Rho GTPases: Promising Cellular Targets for Novel Anticancer Drugs
Current Cancer Drug Targets Anionic Antimicrobial Peptides from Eukaryotic Organisms
Current Protein & Peptide Science One Pot Green Synthesis of Doxorubicin and Curcumin Loaded Magnetic Nanoparticles and Cytotoxicity Studies
Anti-Cancer Agents in Medicinal Chemistry Last Generation of Amino-Bisphosphonates (N-BPs) and Cancer Angiogenesis: A New Role for These Drugs?
Recent Patents on Anti-Cancer Drug Discovery New Insights into the Binding Mechanism of Co-regulator BUD31 to AR AF2 Site: Structural Determination and Analysis of the Mutation Effect
Current Computer-Aided Drug Design Journey of 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU): from Antiviral Drug to PET Imaging Agent
Current Medicinal Chemistry