COLLATERAL SENSITIVIES EMERGE DURING THE EVOLUTION OF CHEMORESISTANCE TO MAP CHEMOTHERAPY IN OSTEOSARCOMA (CTOS 2025) - Nov 23, 2025 - Abstract #P 10; "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..."
Oncology • Osteosarcoma • Sarcoma • Solid Tumor
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Zachary Burke, MD; Gabriel Mandel, MD; Jarrell Imamura, BA (he/him/his); Arda Durmaz, Ph.D.; Masahiro Hitomi, MD, PhD; Jacob G. Scott, MD (he/him/his); Elizabeth Nowak, BS
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