Evangelos Prokakis, Lisa Schneider, Felix Bremmer, Daniel Nettersheim
BACKGROUND: Yolk-sac tumors are an aggressive subtype of testicular cancer that significantly contribute to disease progression and therapy resistance, especially in adults. While testicular cancer generally has high cure rates with cisplatin-based treatment, adult yolk-sac tumors often appear as components of mixed tumors with poor response to therapy and worse outcomes. Pediatric yolk-sac tumors tend to be pure and curable, but adult forms are biologically distinct and more aggressive. OBJECTIVES: This review addresses the urgent clinical challenge posed by this disease by summarizing their pathophysiology, diagnostic biomarkers, and molecular drivers that sustain their aggressive behavior. RESULTS / OUTCOME: By emphasizing key epigenetic and genetic alterations, as well as differentiation programs, this work highlights current and emerging therapeutic strategies aimed at improving early detection and treatment responses. Understanding yolk-sac tumor biology is essential to overcoming resistance and improving survival in patients affected by this high-risk tumor subtype.