299
Views
16
Downloads
1
Crossref
N/A
WoS
1
Scopus
N/A
CSCD
Androgen receptor (AR) signaling have been frequently targeted for treating prostate cancer (PCa). Even though primarily patients receive a good therapeutic outcome by targeting AR signaling axis, eventually it emerges resistance by altering the genetic makeup of prostate cells. However, to develop an effective therapeutic regime, it is essential to recognize key genetic alterations in PCa. The most common genetic alterations that give rise to distinct androgen different differentiation states are gene fusion of TMPRSS2 with ETS family genes, deletion, or mutation of tumor suppressor PTEN and TP53 gene, amplification or splicing of AR, altered DNA repair genes. In this review, we describe key genes and genetic changes that have been recognized to contribute to altered prostate environment.
Androgen receptor (AR) signaling have been frequently targeted for treating prostate cancer (PCa). Even though primarily patients receive a good therapeutic outcome by targeting AR signaling axis, eventually it emerges resistance by altering the genetic makeup of prostate cells. However, to develop an effective therapeutic regime, it is essential to recognize key genetic alterations in PCa. The most common genetic alterations that give rise to distinct androgen different differentiation states are gene fusion of TMPRSS2 with ETS family genes, deletion, or mutation of tumor suppressor PTEN and TP53 gene, amplification or splicing of AR, altered DNA repair genes. In this review, we describe key genes and genetic changes that have been recognized to contribute to altered prostate environment.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33. https://doi.org/10.3322/caac.21708
Barilla S, Lindblom A, Helgadottir HT. Unravelling genetic variants of a Swedish family with high risk of prostate cancer. Hereditary Cancer Clin Pract. 2022;20(1):28. https://doi.org/10.1186/s13053-022-00234-0
Thompson J, Hyytinen ER, Haapala K, Rantala I, Helin HJ, Jänne OA, et al. Androgen receptor mutations in high‐grade prostate cancer before hormonal therapy. Lab Invest. 2003;83(12):1709–13. https://doi.org/10.1097/01.LAB.0000107262.40402.44
Pavel AG, Stambouli D, Gener I, Preda A, Anton G, Baston C. Genetic variant located on chromosome 17p12 contributes to prostate cancer onset and biochemical recurrence. Sci Rep. 2022;12(1):4546. https://doi.org/10.1038/s41598-022-08472-x
Eeles RA, Kote‐Jarai Z, Giles GG, Olama AAA, Guy M, Jugurnauth SK, et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008;40(3):316–21. https://doi.org/10.1038/ng.90
Finch A, Clark R, Vesprini D, Lorentz J, Kim RH, Thain E, et al. An appraisal of genetic testing for prostate cancer susceptibility. NPJ Precision Oncology. 2022;6(1):43. https://doi.org/10.1038/s41698-022-00282-8
Sipeky C, Tammela TLJ, Auvinen A, Schleutker J. Novel prostate cancer susceptibility gene SP6 predisposes patients to aggressive disease. Prostate Cancer Prostatic Dis. 2021;24(4):1158–66. https://doi.org/10.1038/s41391-021-00378-5
McNeal JE. The zonal anatomy of the prostate. Prostate. 1981;2(1):35–49. https://doi.org/10.1002/pros.2990020105
Timms BG. Prostate development: a historical perspective. Differentiation. 2008;76(6):565–77. https://doi.org/10.1111/j.1432-0436.2008.00278.x
Rebello RJ, Oing C, Knudsen KE, Loeb S, Johnson DC, Reiter RE, et al. Prostate cancer. Nat Rev Dis Primers. 2021;7:9. https://doi.org/10.1038/s41572-020-00243-0
Zhou Q, Nie R, Prins GS, Saunders PT, Katzenellenbogen BS, Hess RA. Localization of androgen and estrogen receptors in adult Male mouse reproductive tract. J Androl. 2002;23(6):870–81. https://doi.org/10.1016/0012-1606(88)90260-6
Donjacour AA, Cunha GR. The effect of androgen deprivation on branching morphogenesis in the mouse prostate. Dev Biol. 1988;128(1):1–14. https://doi.org/10.1016/0012-1606(88)90260-6
Shen MM, Abate‐Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010;24(18):1967–2000. https://doi.org/10.1101/gad.1965810
Wang L, Dehm SM, Hillman DW, Sicotte H, Tan W, Gormley M, et al. A prospective genome‐wide study of prostate cancer metastases reveals association of WNT pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate‐prednisone. Ann Oncol. 2018;29(2):352–60. https://doi.org/10.1093/annonc/mdx689
Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20‐69: an autopsy study of 249 cases. In Vivo. 1994;8(3):439–43. PMID: 7803731. https://doi.org/10.1038/ng.3419
Pomerantz MM, Li F, Takeda DY, Lenci R, Chonkar A, Chabot M, et al. The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nat Genet. 2015;47(11):1346–51. https://doi.org/10.1038/ng.3419
Lin C, Yang L, Tanasa B, Hutt K, Ju B, Ohgi KA, et al. Nuclear receptor‐induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell. 2009;139(6):1069–83. https://doi.org/10.1016/j.cell.2009.11.030
Haffner MC, De Marzo AM, Meeker AK, Nelson WG, Yegnasubramanian S. Transcription‐induced DNA double strand breaks: both oncogenic force and potential therapeutic target. Clin Cancer Res. 2011;17(12):3858–64. https://doi.org/10.1158/1078-0432.CCR-10-2044
Heo SH, Choi YJ, Ryoo HM, Cho JY. Expression profiling of ETS and MMP factors in VEGF‐activated endothelial cells: role of MMP‐10 in VEGF‐induced angiogenesis. J Cell Physiol. 2010;224(3):734–42. https://doi.org/10.1002/jcp.22175
Kumar‐Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8(7):497–511. https://doi.org/10.1038/nrc2402
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644–8. https://doi.org/10.1126/science.1117679
Carver BS, Tran J, Chen Z, Carracedo‐Perez A, Alimonti A, Nardella C, et al. ETS rearrangements and prostate cancer initiation. Nature. 2009;457(7231):E1–E3. https://doi.org/10.1038/nature07738
Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene. 2008;27(3):253–63. https://doi.org/10.1038/sj.onc.1210640
Krohn A, Diedler T, Burkhardt L, Mayer PS, De Silva C, Meyer‐Kornblum M, et al. Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion‐positive and fusion‐negative prostate cancer. Am J Pathol. 2012;181(2):401–12. https://doi.org/10.1016/j.ajpath.2012.04.026
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7. https://doi.org/10.1126/science.275.5308.1943
Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, et al. Prostate‐specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell. 2003;4(3):209–21. https://doi.org/10.1016/s1535-6108(03)00215-0
Chen Y, Chi P, Rockowitz S, Iaquinta PJ, Shamu T, Shukla S, et al. ETS factors reprogram the androgen receptor cistrome and prime prostate tumorigenesis in response to PTEN loss. Nat Med. 2013;19(8):1023–9. https://doi.org/10.1038/nm.3216
Salvesan HB, MacDonad N, Ryan A, Jacobs IJ, Lynch ED, Akslen AK, et al. PTEN methylation is associated with tumor state and microsatellite instability in endometrial carcinoma. Int J Cancer. 2001;91(1):22–6. https://doi.org/10.1002/1097-0215(20010101)91:1<22::AID-IJC1002>3.0.CO;2-S
Cunha GR. The role of androgens in the epithelio‐mesenchymal interactions involved in prostatic morphogenesis in embryonic mice. Anat Rec. 1973;175(1):87–96. https://doi.org/10.1002/ar.1091750108
Kallio HML, Hieta R, Latonen L, Brofeldt A, Annala M, Kivinummi K, et al. Constitutively active androgen receptor splice variants AR‐V3, AR‐V7 and AR‐V9 are co‐expressed in castration‐resistant prostate cancer metastases. Br J Cancer. 2018;119(3):347–56. https://doi.org/10.1038/s41416-018-0172-0
Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, et al. Ligand‐independent androgen receptor variants derived from splicing of cryptic exons signify hormone‐refractory prostate cancer. Cancer Res. 2009;69(1):16–22. https://doi.org/10.1158/0008-5472.CAN-08-2764
Barbieri CE, Chinnaiyan AM, Lerner SP, Swanton C, Rubin MA. The emergence of precision urologic oncology: a collaborative review on biomarker‐driven therapeutics. Eur Urol. 2017;71(2):237–46. https://doi.org/10.1016/j.eururo.2016.08.024
Sumanasuriya S, De Bono J. Treatment of advanced prostate cancer‐a review of current therapies and future promise. Cold Spring Harbor Perspect Med. 2018;8(6):a030635. https://doi.org/10.1101/cshperspect.a030635
Zhao D, Lu X, Wang G, Lan Z, Liao W, Li J, et al. Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN‐deficient cancer. Nature. 2017;542(7642):484–8. https://doi.org/10.1038/nature21357.
Shenoy TR, Boysen G, Wang MY, Xu QZ, Guo W, Koh FM, et al. CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error‐prone double‐strand break repair. Ann Oncol. 2017;28(7):1495–507. https://doi.org/10.1093/annonc/mdx165
Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, et al. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov. 2012;2(11):995–1003. https://doi.org/10.1158/2159-8290.CD-12-0222
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Tissue‐based map of the human proteome. Science. 2015;347(6220):1260419. https://doi.org/10.1126/science.1260419
Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, et al. Divergent clonal evolution of castration resistant neuroendocrine prostate cancer. Nat Med. 2016;22(3):298–305. https://doi.org/10.1038/nm.4045
Yousef GM, Obiezu CV, Luo LY, Black MH, Diamandis EP. Prostase/KLK‐L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. Cancer Res. 1999;59(17):4252–56. https://doi.org/10.1006/geno.2000.6346
None.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.