Understanding the crosstalk of molecular factors and signaling pathways reveals novel biomarkers of cisplatin resistance in testicular germ cell tumors

Jan Roska,  Dana Jurkovicova

Abstract:

Testicular germ cell tumors (TGCTs) mostly affect young men, but fortunately belong to well curable solid tumors. Today, different treatment strategies are applied reaching excellent outcomes, and introduction of alternative approach of patient active surveillance or adjuvant chemotherapy after orchiectomy decreases number of unnecessary toxic treatments of young patients. Also for relapsing patients, salvage therapy offers high survival rates. However, small percentages of affected young men do not respond to conventional therapy regimen due to intrinsic or acquired therapy resistance. For closely watching of patients during active surveillance, patients’ stratification due to their prognosis, detection of therapy resistance and early relapse before treatment initiation, reliable molecular biomarkers and diagnostic tools replacing conventional approaches are still needed. Complex understanding of disease development and progression as well as mechanisms of chemoresistance and their epigenetic or chronobiological regulation pre-requisite successful search for such novel biomarkers. In this review, we aimed to highlight the importance of crosstalk of different regulatory mechanisms and their key players affecting treatment response, and focus on their potential as novel molecular biomarkers and/or druggable targets.