The molecular biology of prostate cancer: current understanding and clinical implications

• Published in: Prostate cancer and prostatic diseases 2018-04, Vol.21 (1), p.22-36
• Main Authors: Gandhi, Jason, Afridi, Adil, Vatsia, Sohrab, Joshi, Gargi, Joshi, Gunjan, Kaplan, Steven A., Smith, Noel L., Khan, Sardar Ali
• Format: Article
• Language: English
• Subjects: 631/67/589/466; 631/67/68; Age; Alternative splicing; Androgen receptors; Androgens; Anopheles; Biological markers; Biology; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer genetics; Cancer metastasis; Cancer patients; Cancer Research; Care and treatment; Castration; Chromosome aberrations; Chromosome abnormalities; Copy number; Doors; Gene expression; Gene mutation; Genes; Genetic diversity; Genetic polymorphisms; Genetic research; Genetics; Genomes; Genomics; Health aspects; Health risks; Heredity; Immunotherapy; Life expectancy; Life span; Malignancy; Medical schools; Metastases; Molecular biology; Mutation; Patient outcomes; Prostate cancer; Receptors; Recurrence (Disease); Review Article; Scientific papers; Search engines; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Tumor suppressor genes; Tumorigenesis; Tumors
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/s41391-017-0023-8

Background With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. Methods A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Results Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. Conclusions An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.