New Prognostic Markers and Potential Therapeutic Targets in Human Testicular Germ Cell Tumors

P.      Chieffi

Abstract

Although testicular germ cell tumors (TGCTs) are relatively uncommon, they are particularly important as they tend to affect children and young men, representing the most common tumor in male aged from 20 to 40 years, and the incidence has been increasing over the last decades. TGCTs are a heterogeneous group of tumors, with specific peculiarities reflecting on epidemiologic distribution and clinic-pathological features. Seminomas are highly sensitive to both radiation and chemotherapy, with a good prognosis, non- seminomas are sensitive to platinum-based combination chemotherapy and are less susceptible to radiation, with the exception of teratomas. However, up to 30% of patients diagnosed with metastatic nonseminomas do not achieve a durable remission, and in metastatic teratomas cisplatin-based treatment resistance has been observed. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originate. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the PGCs/gonocytes, from which these tumours originate.

In the last years novel markers, including OCT3/4, SOX2, SOX17, HMGA1, HMGA2, PATZ1, GPR30, Aurora B, and others has given further advantages to discriminate between histological subgroups. In addition, therapeutic approaches for the treatment of TGCTs have been proposed: humanized antibodies against receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and tyrosine kinases, angiogenesis inhibitors, and others. In same cases the clinical trials have confirmed the efficacy of these approaches.

The review will focus on the molecular alteration identified in post-puberal TGCTs and on novel targeted antineoplastic strategies that could contribute to the cure of chemotherapy resistant TGCTs.

Keywords: Testis, Testicular cancer, Gonocytes, Testicular germ cells tumors, seminomas, teratoma, HMGA, Aurora B, GPR30, PATZ1