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  • Title: Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors.
    Author: Lengert AVH, Pereira LDNB, Cabral ERM, Gomes INF, Jesus LM, Gonçalves MFS, Rocha AOD, Tassinari TA, Silva LSD, Laus AC, Vidal DO, Pinto MT, Reis RM, Lopes LF.
    Journal: Front Biosci (Landmark Ed); 2022 Aug 16; 27(8):245. PubMed ID: 36042160.
    Abstract:
    BACKGROUND: Testicular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. METHODS: In vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. RESULTS: We found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. CONCLUSIONS: MG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.
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