High-Throughput Drug Screening in Chondrosarcoma Cells Identifies Effective Antineoplastic Agents Independent of IDH Mutation.

International journal of molecular sciences [Int J Mol Sci] 2024 Dec 03; Vol. 25 (23). Date of Electronic Publication: 2024 Dec 03.

The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date. Although the role of conventional chemotherapy is still subject to debate, some evidence suggests it may provide therapeutic benefits in advanced cases. In this study, we aimed to identify effective compounds for combination therapy in chondrosarcoma. Using high-throughput screening, we evaluated a panel of anticancer agents in IDH1-mutant chondrosarcoma cell lines and their mutant IDH1 knockout derivatives. The top 20 most potent compounds were identified across all cell lines, irrespective of IDH mutation status. Representative drugs selected for further investigation included docetaxel, methotrexate, panobinostat, idarubicin, camptothecin, and pevonedistat. These drugs inhibited colony formation, induced apoptosis and cell cycle arrest, and exhibited synergistic antitumor activity in two-drug combinations. In conclusion, we identified several highly effective agents with potent anti-tumor activity in chondrosarcoma cells, independent of IDH mutation status. These agents represent promising candidates for chondrosarcoma therapy and warrant further preclinical investigation and potential inclusion in clinical trials.

English

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Isocitrate Dehydrogenase*/genetics , Isocitrate Dehydrogenase*/antagonists & inhibitors , Chondrosarcoma*/genetics , Chondrosarcoma*/drug therapy , Mutation* , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/therapeutic use , High-Throughput Screening Assays*/methods, Humans ; Cell Line, Tumor ; Drug Screening Assays, Antitumor/methods ; Apoptosis/drug effects ; Bone Neoplasms/drug therapy ; Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Drug Synergism ; Cell Proliferation/drug effects

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