Collateral Sensitivities Emerge During the Evolution of Chemoresistance to Map Chemotherapy in Osteosarcoma (NCCN 2026) - Mar 31, 2026 - Abstract #YIA26-001; "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...Collateral resistance emerged to etoposide, topotecan, and cabozantinib, while sensitivity increased to palifosfamide, vorinostat, and gemcitabine/docetaxel... 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 palifosfamide, vorinostat, and gemcitabine/docetaxel supports a second line use for these agents. Our model can form the basis of transcriptionally guided second line therapy to preempt or exploit resistance evolution."
Osteosarcoma • Sarcoma • Solid Tumor
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Zachary Burke; Gabe Mandel; Elizabeth Nowak; Jarrell Imamura; Arda Durmaz; Masahiro Hitomi; Jacob Scott
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