Silvia Schmidtova1, Katarina Kalavska1,2,3, Lucia Kucerova4. 1. Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05, Bratislava, Slovakia. 2. 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenová 1, 833 10, Bratislava, Slovakia. 3. Translational Research Unit, Faculty of Medicine, Comenius University, Klenová 1, Bratislava, 833 10, Slovakia. 4. Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05, Bratislava, Slovakia. lucia.kucerova@savba.sk.
Abstract
PURPOSE OF REVIEW: Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. Majority of TGCTs respond well to cisplatin-based chemotherapy. However, patients with refractory disease have limited treatment modalities associated with poor prognosis. Here, we discuss the main molecular mechanisms associated with acquired cisplatin resistance in TGCTs and how their understanding might help in the development of new approaches to tackle this clinically relevant problem. We also discuss recent data on the strategies of circumventing the cisplatin resistance from different tumor types potentially efficient also in TGCTs. RECENT FINDINGS: Recent data regarding deregulation of various signaling pathways as well as genetic and epigenetic mechanisms in cisplatin-resistant TGCTs have contributed to understanding of the mechanisms related to the resistance to cisplatin-based chemotherapy in these tumors. Understanding of these mechanisms enabled explaining why majority but not all TGCTs patients are curable with cisplatin-based chemotherapy. Moreover, it could lead to the development of more effective treatment of refractory TGCTs and potentially other solid tumors resistant to platinum-based chemotherapy. This review provides additional insights into mechanisms associated with cisplatin resistance in TGCTs, which is a complex phenomenon, and there is a need for novel modalities to overcome it.
PURPOSE OF REVIEW: Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. Majority of TGCTs respond well to cisplatin-based chemotherapy. However, patients with refractory disease have limited treatment modalities associated with poor prognosis. Here, we discuss the main molecular mechanisms associated with acquired cisplatin resistance in TGCTs and how their understanding might help in the development of new approaches to tackle this clinically relevant problem. We also discuss recent data on the strategies of circumventing the cisplatin resistance from different tumor types potentially efficient also in TGCTs. RECENT FINDINGS: Recent data regarding deregulation of various signaling pathways as well as genetic and epigenetic mechanisms in cisplatin-resistant TGCTs have contributed to understanding of the mechanisms related to the resistance to cisplatin-based chemotherapy in these tumors. Understanding of these mechanisms enabled explaining why majority but not all TGCTs patients are curable with cisplatin-based chemotherapy. Moreover, it could lead to the development of more effective treatment of refractory TGCTs and potentially other solid tumors resistant to platinum-based chemotherapy. This review provides additional insights into mechanisms associated with cisplatin resistance in TGCTs, which is a complex phenomenon, and there is a need for novel modalities to overcome it.
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