Abstract
The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggest that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tumors. Recent data indicate that testicular cancer cells, even those resistant to platinum, are highly sensitive to low doses of demethylating agents. Based on these promising preclinical studies, we suggest that DNA methylation inhibitors in combination with chemotherapeutic agents may offer a path to overcome acquired drug resistance in testicular cancer, laying the foundation and rationale for testing this class of epigenetic drugs in the clinical setting. In this mini-review we provide a brief overview of the promise of DNA methylation therapy to treat patients with refractory cancer of the testes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 789-795 |
| Number of pages | 7 |
| Journal | Current Cancer Drug Targets |
| Volume | 16 |
| Issue number | 9 |
| DOIs | |
| State | Published - Nov 1 2016 |
| Externally published | Yes |
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Keywords
- Cisplatin resistance
- DNA methyltransferase
- Decitabine
- Embryonal carcinoma
- Epigenetics
- Germ cell tumor
- SGI-110
- Testicular cancer
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Drug Discovery
- Cancer Research
Cite this
Epigenetic targeting of platinum resistant testicular cancer. / Sonnenburg, Daniel; Spinella, Michael J.; Albany, Costantine.
In: Current Cancer Drug Targets, Vol. 16, No. 9, 01.11.2016, p. 789-795.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Epigenetic targeting of platinum resistant testicular cancer
AU - Sonnenburg, Daniel
AU - Spinella, Michael J.
AU - Albany, Costantine
PY - 2016/11/1
Y1 - 2016/11/1
N2 - The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggest that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tumors. Recent data indicate that testicular cancer cells, even those resistant to platinum, are highly sensitive to low doses of demethylating agents. Based on these promising preclinical studies, we suggest that DNA methylation inhibitors in combination with chemotherapeutic agents may offer a path to overcome acquired drug resistance in testicular cancer, laying the foundation and rationale for testing this class of epigenetic drugs in the clinical setting. In this mini-review we provide a brief overview of the promise of DNA methylation therapy to treat patients with refractory cancer of the testes.
AB - The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggest that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tumors. Recent data indicate that testicular cancer cells, even those resistant to platinum, are highly sensitive to low doses of demethylating agents. Based on these promising preclinical studies, we suggest that DNA methylation inhibitors in combination with chemotherapeutic agents may offer a path to overcome acquired drug resistance in testicular cancer, laying the foundation and rationale for testing this class of epigenetic drugs in the clinical setting. In this mini-review we provide a brief overview of the promise of DNA methylation therapy to treat patients with refractory cancer of the testes.
KW - Cisplatin resistance
KW - DNA methyltransferase
KW - Decitabine
KW - Embryonal carcinoma
KW - Epigenetics
KW - Germ cell tumor
KW - SGI-110
KW - Testicular cancer
UR - http://www.scopus.com/inward/record.url?scp=84995642781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995642781&partnerID=8YFLogxK
U2 - 10.2174/1568009616666151222150359
DO - 10.2174/1568009616666151222150359
M3 - Review article
C2 - 26694252
AN - SCOPUS:84995642781
VL - 16
SP - 789
EP - 795
JO - Current Cancer Drug Targets
JF - Current Cancer Drug Targets
SN - 1568-0096
IS - 9
ER -