Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells

Overview

Journal Curr Cancer Ther Rev

Publisher Bentham Science Publishers

Specialty Oncology

Date 2014 Feb 1

PMID 24482633

Citations 16

Authors

Caryl J Giuliano

Sarah J Freemantle

Michael J Spinella

Affiliations

Soon will be listed here.

Abstract

Treatment of testicular germ cell tumors (TGCTs) has been a success primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy. Despite the promise of cure for the majority of TGCT patients, the effectiveness of therapy for some patients is limited by toxicity and the problem of resistance. There is compelling rationale to further understand the biology of TGCTs in order to better treat other solid tumors and to address the shortcomings of present TGCT therapies. TGCTs contain undifferentiated pluripotent stem cells, known as embryonal carcinoma, that share many properties with human embryonic stem cells. The importance of cancer stem cells in the initiation, progression and treatment of solid tumors is beginning to emerge. We discuss TGCTs in the context of solid tumor curability and targeted cancer stem cell therapy.

Citing Articles

Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.

Cuevas-Estrada B, Montalvo-Casimiro M, Munguia-Garza P, Rios-Rodriguez J, Gonzalez-Barrios R, Herrera L Int J Mol Sci. 2023; 24(9).

PMID: 37175579 PMC: 10178517. DOI: 10.3390/ijms24097873.

Quantitative analysis of signaling responses during mouse primordial germ cell specification.

Morgani S, Hadjantonakis A Biol Open. 2021; 10(5).

PMID: 34184730 PMC: 8186728. DOI: 10.1242/bio.058741.

Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.

Singh R, Fazal Z, Freemantle S, Spinella M Cancers (Basel). 2021; 13(7).

PMID: 33805941 PMC: 8036638. DOI: 10.3390/cancers13071506.

A phase 1 study of combined guadecitabine and cisplatin in platinum refractory germ cell cancer.

Albany C, Fazal Z, Singh R, Bikorimana E, Adra N, Hanna N Cancer Med. 2020; 10(1):156-163.

PMID: 33135391 PMC: 7826483. DOI: 10.1002/cam4.3583.

Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives.

Lobo J, Jeronimo C, Henrique R Cancers (Basel). 2020; 12(6).

PMID: 32560427 PMC: 7352163. DOI: 10.3390/cancers12061601.

References

Youngren K, Coveney D, Peng X, Bhattacharya C, Schmidt L, Nickerson M . The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours. Nature. 2005; 435(7040):360-4. PMC: 1421521. DOI: 10.1038/nature03595. View

Hussain A . Germ cell tumors. Curr Opin Oncol. 2005; 17(3):268-74. DOI: 10.1097/01.cco.0000160750.33552.42. View

Sark M, Timmer-Bosscha H, Meijer C, Uges D, Sluiter W, Peters W . Cellular basis for differential sensitivity to cisplatin in human germ cell tumour and colon carcinoma cell lines. Br J Cancer. 1995; 71(4):684-90. PMC: 2033748. DOI: 10.1038/bjc.1995.135. View

Burger H, Nooter K, Boersma A, Kortland C, Stoter G . Lack of correlation between cisplatin-induced apoptosis, p53 status and expression of Bcl-2 family proteins in testicular germ cell tumour cell lines. Int J Cancer. 1997; 73(4):592-9. DOI: 10.1002/(sici)1097-0215(19971114)73:4<592::aid-ijc22>3.0.co;2-a. View

Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, Boiani M . Oct4 is required for primordial germ cell survival. EMBO Rep. 2004; 5(11):1078-83. PMC: 1299174. DOI: 10.1038/sj.embor.7400279. View

Almstrup K, Hoei-Hansen C, Wirkner U, Blake J, Schwager C, Ansorge W . Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res. 2004; 64(14):4736-43. DOI: 10.1158/0008-5472.CAN-04-0679. View

Rodriguez E, Houldsworth J, Reuter V, Meltzer P, Zhang J, Trent J . Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors. Genes Chromosomes Cancer. 1993; 8(4):230-6. DOI: 10.1002/gcc.2870080405. View

Valk-Lingbeek M, Bruggeman S, van Lohuizen M . Stem cells and cancer; the polycomb connection. Cell. 2004; 118(4):409-18. DOI: 10.1016/j.cell.2004.08.005. View

Okada K, Katagiri T, Tsunoda T, Mizutani Y, Suzuki Y, Kamada M . Analysis of gene-expression profiles in testicular seminomas using a genome-wide cDNA microarray. Int J Oncol. 2003; 23(6):1615-35. View

10.

Dumont P, Leu J, Della Pietra 3rd A, George D, Murphy M . The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003; 33(3):357-65. DOI: 10.1038/ng1093. View

11.

Curtin J, Dragnev K, Sekula D, Christie A, Dmitrovsky E, Spinella M . Retinoic acid activates p53 in human embryonal carcinoma through retinoid receptor-dependent stimulation of p53 transactivation function. Oncogene. 2001; 20(20):2559-69. DOI: 10.1038/sj.onc.1204370. View

12.

Boekelheide K . Mechanisms of toxic damage to spermatogenesis. J Natl Cancer Inst Monogr. 2005; (34):6-8. DOI: 10.1093/jncimonographs/lgi006. View

13.

Looijenga L, Oosterhuis J . Pathobiology of testicular germ cell tumors: views and news. Anal Quant Cytol Histol. 2002; 24(5):263-79. View

14.

Hoei-Hansen C, Almstrup K, Nielsen J, Brask Sonne S, Graem N, Skakkebaek N . Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. 2005; 47(1):48-56. DOI: 10.1111/j.1365-2559.2005.02182.x. View

15.

Oosterhuis J, Looijenga L . Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer. 2005; 5(3):210-22. DOI: 10.1038/nrc1568. View

16.

Jones R, Vasey P . New directions in testicular cancer; molecular determinants of oncogenesis and treatment success. Eur J Cancer. 2003; 39(2):147-56. DOI: 10.1016/s0959-8049(02)00612-3. View

17.

Lutzker S, Mathew R, Taller D . A p53 dose-response relationship for sensitivity to DNA damage in isogenic teratocarcinoma cells. Oncogene. 2001; 20(23):2982-6. DOI: 10.1038/sj.onc.1204394. View

18.

Draper J, Smith K, Gokhale P, Moore H, Maltby E, Johnson J . Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol. 2003; 22(1):53-4. DOI: 10.1038/nbt922. View

19.

Mauduit C, Hamamah S, Benahmed M . Stem cell factor/c-kit system in spermatogenesis. Hum Reprod Update. 1999; 5(5):535-45. DOI: 10.1093/humupd/5.5.535. View

20.

Rajpert-De Meyts E, Kvist M, Skakkebaek N . Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ: pathogenetic relevance. Virchows Arch. 1996; 428(3):133-9. DOI: 10.1007/BF00200655. View