Title:Epigenetic Targeting of Platinum Resistant Testicular Cancer
Volume: 16
Issue: 9
Author(s): Daniel Sonnenburg, Michael J. Spinella, Costantine Albany
Affiliation:
关键词:
睾丸癌、生殖细胞瘤、胚胎癌，顺铂耐药，表观遗传学，DNA甲基转移酶，地西他滨，SGI-110
摘要: 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.
