Molecular and epigenetic deciphering of somatic-type malignancies and growing teratoma syndrome to establish new therapeutic options for therapy-resistant germ cell tumors.

• Applicant: Dr. Pailin Pongratanakul
• Subject Area: Reproductive Medicine, Urology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560311098

Testicular type II germ cell tumors (GCT) represent the most common tumor of young men of age 17 - 45 years and incidence rates are rising steadily. Type II GCTs can be stratified into seminomas and non-seminomas, which both arise from the precursor lesion germ cell neoplasia in situ (GCNIS) as a result of a defective primordial germ cell (PGC) development. The non-seminomas have their own stem cell population - the embryonal carcinoma (EC). EC are pluripotent and able to differentiate into cells of all three germ layers, resulting in formation of teratomas (TER), and into extra-embryonic tissues, i. e. yolk-sac tumors (YST) and choriocarcinomas (CC). A deadly subtype of GCT is the somatic-type malignancy (STM), a secondary tumor component of non-seminomas that resembles cancers seen in other organs and tissues. These STM span a wide variety of tumors, including rhabdomyosarcomas or adenocarcinomas. STM occur with an incidence of 2-6 % at any point of GCT development, but are mainly diagnosed at a metastatic stage in a post-chemotherapeutic setting. Patients with STM face a 5-year survival rate of 50-60 % due to resistance towards cisplatin-based chemotherapy. In 1982, Logothetis et al. first described an unusual phenomenon called the ‘growing teratoma syndrome’ (GTS). During cisplatin-based standard chemotherapy, some patients present with a growing tumor mass on imaging, while routine serum tumor markers are decreasing or normalized. In these cases, complete surgical resection represents the only treatment option, revealing pure teratoma without evidence of other GCT entities in the final pathology. Both, STM and GTS are special forms of GCT affecting mostly young men and having a poor prognosis. So far, specific treatment options or biomarkers early detecting STM / GTS are still lacking, further research on their pathogenesis and the identification of potential therapeutic targets is warranted. In this study, we address these clinical needs by 1) analyzing the epigenetic landscape of histone modifications and the activity of signaling pathways by a mass spectrometry based approach in order to deduce new therapeutic options and test them in ex-vivo cultures and 2) screen novel liquid biomarkers deduced from previous studies in patients’ blood serum samples. By this, we will not only shed light on the molecular and epigenetic features of STM / GTS and deepen the knowledge on development of STM / GTS, but also deduce and screen novel therapeutic options and liquid biomarkers for future clinical trials and pathological routine diagnostics, respectively.

• DFG Programme: Research Grants