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

被引:58
作者
Gandhi, Jason [1 ,2 ]
Afridi, Adil [1 ]
Vatsia, Sohrab [3 ]
Joshi, Gargi [1 ]
Joshi, Gunjan [4 ]
Kaplan, Steven A. [5 ,6 ]
Smith, Noel L. [7 ]
Khan, Sardar Ali [1 ,8 ]
机构
[1] SUNY Stony Brook, Sch Med, Dept Physiol & Biophys, Stony Brook, NY 11794 USA
[2] St Georges Univ, Sch Med, Med Student Res Inst, St Georges, Grenada
[3] Lenox Hill Hosp, Dept Cardiothorac Surg, New York, NY 10021 USA
[4] Southampton Hosp, Stony Brook Med, Dept Internal Med, Southampton, NY USA
[5] Icahn Sch Med Mt Sinai, Dept Urol, New York, NY 10029 USA
[6] Mt Sinai Hlth Syst, Mens Wellness Program, New York, NY USA
[7] Foley Plaza Med, New York, NY USA
[8] SUNY Stony Brook, Sch Med, Dept Urol, Stony Brook, NY 11794 USA
关键词
GENOME-WIDE ASSOCIATION; TUMOR-SUPPRESSOR GENE; AFRICAN-AMERICAN MEN; DNA MISMATCH REPAIR; LONG NONCODING RNA; ENGINEERED T-CELLS; SUSCEPTIBILITY LOCI; ANDROGEN RECEPTOR; INCREASED EXPRESSION; GERMLINE MUTATIONS;
D O I
10.1038/s41391-017-0023-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (R) 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.
引用
收藏
页码:22 / 36
页数:15
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