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bioRxiv · 10.1101/2023.10.19.563192

Chemo-senolytic therapeutic potential against angiosarcoma

Wang, X.·Chung, C. Y.-L.·Yoshioka, A.·Hashimoto, S.·Jimbo, H.·Tanizawa, H.·Ohta, S.·Fukumoto, T.·Noma, K.-i.
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Abstract

Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype (SASP) genes are activated in senescent angiosarcoma cells and that ABT-263 treatment eliminates senescent cells expressing genes in the type-I interferon (IFN-I) pathway. Moreover, we show that cisplatin treatment alone requires a high dose to remove angiosarcoma cells, whereas a lower dose of cisplatin is sufficient to induce senescence, followed by the elimination of senescent cells by senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.

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Wang, X., Chung, C. Y.-L., Yoshioka, A., Hashimoto, S., Jimbo, H., Tanizawa, H., Ohta, S., Fukumoto, T., Noma, K.-i.. 2023-10-20. Chemo-senolytic therapeutic potential against angiosarcoma. https://doi.org/10.1101/2023.10.19.563192

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