P48 - Drug response profiling of adrenocortical carcinoma in vitro models reveals differential sensitivity to cisplatin and etoposide

Background/Introduction Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with limited therapeutic options in advanced stages. The standard first-line therapy (EDP-M) combines mitotane with etoposide, doxorubicin, and cisplatin, achieving response rates around 53%. However, a comprehensive evaluation of cisplatin and etoposide effects across the currently available ACC cell models is still lacking. Purpose To investigate the cellular response to cisplatin and etoposide in ACC in vitro models. Methods We tested a panel of five human ACC cell lines: H295R and JIL-2266, derived from primary tumors, and CU-ACC1, CU-ACC2, and TVBF-7 derived from perinephric, liver, and lymph node metastases, respectively. In addition, we tested three patients-derived primary ACC cell cultures: one from a primary tumor and two derived respectively from a peritoneal and a lung metastasis. Drug sensitivity was evaluated by measuring cell viability via ATP quantification after 72 hours of drug incubation. Results H295R and JIL-2266 cells responded to both cisplatin and etoposide. While H295R cells exhibited moderate sensitivity, with IC50 values of 9.67 µM for cisplatin and 10.21 µM for etoposide, JIL-2266 cells were markedly more sensitive, showing significantly lower IC50 values (0.61 µM for cisplatin and 0.36 µM for etoposide). Among the metastatic-derived cell lines, CU-ACC2 responded to both agents but showed greater sensitivity to cisplatin (IC50=3.35 µM) compared to etoposide (IC50=9.65 µM). In contrast, both ACC1 and TVBF-7 cells were completely unresponsive to etoposide at all tested concentrations and responded to cisplatin with an IC50 of 6.32 µM and 2.09 µM, respectively. Cisplatin treatment led to reduced cell viability in all three primary cultures, though with variable sensitivities. The lung metastasis-derived culture was the most responsive to cisplatin (IC50=1.32 µM), while the primary tumor and peritoneal metastasis showed higher IC50 values (10.43 µM and 11.31 µM, respectively). Notably, the lung metastatic culture also responded to etoposide at low concentrations. Conclusion(s) In conclusion, we observed heterogeneous drug responses across ACC models, independent of their primary or metastatic origin. All IC50 values fell within clinically relevant micromolar ranges, supporting the translational value of these models for therapeutic testing.