Expert opinion on therapeutic targets · 2025
Potential therapeutic targets and biomarkers in testicular germ cell tumor oncogenesis.
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Esposito Francesco, De Martino Marco, Franco Viviana, Fusco Alfredo, Chieffi Paolo
Аннотация
INTRODUCTION: The most prevalent solid cancer in young adult males is testicular germ cell tumors (TGCTs), which are becoming more and more common globally. Approximately 20% of patients with metastatic disease relapse or develop resistance to cisplatin-based chemotherapy, despite its high effectiveness, underscoring the need for alternative therapies.
AREAS COVERED: With an emphasis on new molecular targets and biomarkers, this review describes developments in TGCT pathophysiology and treatment. Tyrosine kinase receptors, transcription factors, elements of the DNA damage response, and cell cycle regulators are important oncogenic drivers. CDK inhibitors, PARP inhibitors, and Aurora kinase antagonists are promising early-stage agents. Meanwhile, noninvasive liquid biopsy techniques are being made possible by biomarkers like CLDN6, cfDNA/ctDNA, and the miR-371 ~ 373 cluster, which may enhance disease monitoring, risk assessment, and diagnosis.
EXPERT OPINION: Although the majority of TGCT cases have positive results, cisplatin-refractory disease continues to be a significant therapeutic challenge. A route to precision medicine is provided by molecular profiling and biomarker-driven approaches. However, implementation requires clinical validation, patient selection, and standardization. The landscape of TGCT treatment may change over the next 10 years as a result of the integration of targeted therapies and molecular diagnostics, which may greatly increase survival rates while lowering long-term toxicity.
AREAS COVERED: With an emphasis on new molecular targets and biomarkers, this review describes developments in TGCT pathophysiology and treatment. Tyrosine kinase receptors, transcription factors, elements of the DNA damage response, and cell cycle regulators are important oncogenic drivers. CDK inhibitors, PARP inhibitors, and Aurora kinase antagonists are promising early-stage agents. Meanwhile, noninvasive liquid biopsy techniques are being made possible by biomarkers like CLDN6, cfDNA/ctDNA, and the miR-371 ~ 373 cluster, which may enhance disease monitoring, risk assessment, and diagnosis.
EXPERT OPINION: Although the majority of TGCT cases have positive results, cisplatin-refractory disease continues to be a significant therapeutic challenge. A route to precision medicine is provided by molecular profiling and biomarker-driven approaches. However, implementation requires clinical validation, patient selection, and standardization. The landscape of TGCT treatment may change over the next 10 years as a result of the integration of targeted therapies and molecular diagnostics, which may greatly increase survival rates while lowering long-term toxicity.