Evolving toward precision oncology: Leveraging collateral drug responses for personalized second-line osteosarcoma treatment (AACR 2026) - Mar 18, 2026 - Abstract #3542/18; Pres time: Apr 20, 2026; 02:00 PM - 05:00 PM; Location: Section 33; "Objective: We aimed to model the evolution of chemoresistance to methotrexate, doxorubicin, and cisplatin (MAP) in vitro and to characterize collateral drug sensitivity and resistance patterns over time, potentially informing second-line treatment strategies in chemo resistant primary or recurrent disease. Five evolutionary replicates of MG63.3 osteosarcoma cells were treated with six complete cycles of pulsed, clinically relevant doses of cisplatin and doxorubicin, alternating with methotrexate...Collateral resistance emerged to etoposide, vincristine, and topotecan, while sensitivity increased to gemcitabine, cabozantinib, and palifosfamide... Our model reveals temporally dynamic, heterogeneous collateral responses during the development of chemoresistance to MAP in osteosarcoma. While cross-resistance to several agents emerged, collateral sensitivity to gemcitabine and cabozantinib supports a second line use for these agents. These data may inform rational..."
Clinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor
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Elizabeth Nowak1; Jarrell Imamura2; Arda Durmaz1; Masahiro Hitomi3; Zachary Burke1; Jacob G. Scott4
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