Abstract
Testicular cancer is an aggressive malignancy with a rising incidence rate across the globe. Testicular germ cell tumors are the most commonly diagnosed cancers, and surgical removal of the testes is often a radical necessity along with chemotherapy and radiotherapy. While seminomas are receptive to radiotherapy as well as chemotherapy, non-seminomatous germ cell tumors respond to chemotherapy only. Due to the singular nature of testicular cancers with associated orchiectomy and mortality, it is important to study the molecular basis and genetic underpinnings of this group of cancers across male populations globally. In this review, we shed light on the population pharmacogenetics of testicular cancer, pediatric and adult tumors, current clinical trials, genetic determinants of chemotherapy-induced toxicity in testicular cancer, as well as the molecular signal transduction pathways operating in this malignancy. Taken together, our discussions will help in enhancing our understanding of genetic factors in testicular carcinogenesis and chemotherapy-induced toxicity, augment our knowledge of this aggressive cancer at the cellular and molecular level, as well as improve precision medicine approaches to combat this disease.
Keywords: Variant polymorphism, Pharmacogenetics, Population pharmacogenetics, Precision medicine, Testicular seminoma, Testicular cancer, Ethnicity, Pharmacogenomics, Toxicity, Clinical trials, Molecular aspects, Signal transduction.
[PMID: 27885307]
[http://dx.doi.org/10.1016/j.canep.2018.05.007 PMID: 29807233]
[PMID: 26816836]
[http://dx.doi.org/10.1155/2018/2375176 PMID: 29662516]
[http://dx.doi.org/10.1016/j.eururo.2016.02.029 PMID: 26935559]
[http://dx.doi.org/10.1007/s00428-013-1522-1]
[http://dx.doi.org/10.1016/j.jons.2017.10.002]
[http://dx.doi.org/10.1007/978-3-662-53775-6_7]
[http://dx.doi.org/10.1016/j.ucl.2015.04.002 PMID: 26216815]
[http://dx.doi.org/10.1016/B978-0-12-801238-3.64814-6]
[http://dx.doi.org/10.1172/jci.insight.86837] [PMID: 27699219]
[http://dx.doi.org/10.1093/humrep/det127] [PMID: 23639623]
[http://dx.doi.org/10.3892/mmr.2017.6822] [PMID: 28656227]
[http://dx.doi.org/10.1038/35101056] [PMID: 11905809]
[http://dx.doi.org/10.1046/j.0306-5251.2001.01498.x] [PMID: 11678777]
[http://dx.doi.org/10.1007/s13167-017-0080-z PMID: 28620445]
[http://dx.doi.org/10.1039/C6MB00115G] [PMID: 27066891]
[http://dx.doi.org/10.1016/j.ejca.2015.11.009] [PMID: 26751392]
[http://dx.doi.org/10.1097/FPC.0b013e3283396c4e] [PMID: 20393316]
[http://dx.doi.org/10.1038/tpj.2014.22] [PMID: 24861855]
[http://dx.doi.org/10.1093/mutage/geu088] [PMID: 25690281]
[http://dx.doi.org/10.1186/s12957-017-1142-3] [PMID: 28388903]
[http://dx.doi.org/10.1007/s13277-011-0314-y] [PMID: 22249976]
[http://dx.doi.org/10.1016/j.lungcan.2012.03.023] [PMID: 22516052]
[http://dx.doi.org/10.1093/abbs/gmq023]
[http://dx.doi.org/10.1016/S0959-8049(05)80106-6]
[http://dx.doi.org/10.1097/FPC.0b013e328323f680] [PMID: 19214144]
[http://dx.doi.org/10.1093/jjco/hym165] [PMID: 18250203]
[http://dx.doi.org/10.1097/FPC.0000000000000182] [PMID: 26444257]
[http://dx.doi.org/10.1371/journal.pone.0099843]
[http://dx.doi.org/10.1186/1476-4598-9-248] [PMID: 20846399]
[http://dx.doi.org/10.1007/s13277-014-1959-0] [PMID: 24793015]
[http://dx.doi.org/10.1016/j.forsciint.2010.09.017] [PMID: 20951518]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0344] [PMID: 19622575]
[http://dx.doi.org/10.1016/j.cell.2013.09.017] [PMID: 24120139]
[http://dx.doi.org/10.1007/s40262-016-0450-z] [PMID: 27641154]
[http://dx.doi.org/10.7314/APJCP.2015.16.11.4659]
[http://dx.doi.org/10.1371/journal.pone.0079864]
[http://dx.doi.org/10.1007/s13277-015-4317-y]
[http://dx.doi.org/10.1111/php.12617] [PMID: 27400420]
[http://dx.doi.org/10.1001/jamaoncol.2017.0502]
[http://dx.doi.org/10.1038/tpj.2016.52]
[http://dx.doi.org/10.1200/JCO.2016.68.7798]
[http://dx.doi.org/10.1007/s12288-014-0482-1]
[http://dx.doi.org/10.1371/journal.pone.0078071] [PMID: 24205095]
[http://dx.doi.org/10.1016/j.ejca.2018.03.004] [PMID: 29859339]
[http://dx.doi.org/10.1097/MPH.0b013e3182707fc5]
[http://dx.doi.org/10.1038/s41416-018-0277-5] [PMID: 30287918]
[http://dx.doi.org/10.1016/j.taap.2017.04.013] [PMID: 28414026]
[http://dx.doi.org/10.1038/clpt.2009.139] [PMID: 19625999]
[http://dx.doi.org/10.1007/s10157-012-0638-y] [PMID: 22569819]
[http://dx.doi.org/10.3389/fphar.2015.00085]
[http://dx.doi.org/10.1620/tjem.219.177] [PMID: 19851045]
[http://dx.doi.org/10.4103/1008-682X.191126]
[http://dx.doi.org/10.1200/JCO.2007.14.1606]
[http://dx.doi.org/10.1016/j.ejca.2016.02.013]
[http://dx.doi.org/10.1155/2016/8235121] [PMID: 28083147]
[http://dx.doi.org/10.17352/gjct.000001]
[http://dx.doi.org/10.4137/BIC.S19681]
[PMID: 25867573]
[http://dx.doi.org/10.7326/0003-4819-95-3-288]
[http://dx.doi.org/10.1186/1479-5876-5-70]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-2244] [PMID: 30305294]
[http://dx.doi.org/10.1038/nrc3983] [PMID: 26289315]
[http://dx.doi.org/10.3389/fendo.2013.00032] [PMID: 23519268]
[http://dx.doi.org/10.1016/j.bbrc.2005.09.042] [PMID: 16188233]
[http://dx.doi.org/10.1038/modpathol.3800309] [PMID: 15761466]
[http://dx.doi.org/10.1007/s12079-017-0399-1] [PMID: 28656507]
[http://dx.doi.org/10.1002/gcc.20562] [PMID: 18381640]
[http://dx.doi.org/10.1016/j.taap.2005.01.058] [PMID: 16005920]
[http://dx.doi.org/10.1093/humrep/16.5.972] [PMID: 11331648]
[http://dx.doi.org/10.1016/0165-4608(92)90316-Z] [PMID: 1458445]
[http://dx.doi.org/10.1016/S0002-9440(10)63120-3] [PMID: 14695343]
[PMID: 2682461]
[http://dx.doi.org/10.1002/gcc.2870010307] [PMID: 1964583]
[PMID: 8143614]
[http://dx.doi.org/10.17305/bjbms.2017.1764] [PMID: 28426398]
[http://dx.doi.org/10.1016/j.canlet.2016.04.016] [PMID: 27085458]
[http://dx.doi.org/10.1038/bjc.1991.189] [PMID: 1829952]
[http://dx.doi.org/10.1002/jcp.25482] [PMID: 27405110]
[http://dx.doi.org/10.1002/jcp.24328] [PMID: 23359388]
[PMID: 28871003]
[http://dx.doi.org/10.7150/jca.17579] [PMID: 28367242]
[PMID: 22432056]
[http://dx.doi.org/10.2741/4534] [PMID: 28199193]
[http://dx.doi.org/10.1016/j.bbrc.2018.06.047] [PMID: 29902454]
[http://dx.doi.org/10.1038/onc.2013.512] [PMID: 24292675]
[http://dx.doi.org/10.1111/cas.13105]
[http://dx.doi.org/10.18632/oncotarget.13624] [PMID: 27902973]
[http://dx.doi.org/10.1002/gcc.20520] [PMID: 18050305]
[http://dx.doi.org/10.18632/oncotarget.20992] [PMID: 29262668]
[http://dx.doi.org/10.1515/dmpt-2018-0008] [PMID: 29688886]
[http://dx.doi.org/10.1007/s40495-018-0139-0] [PMID: 30345221]