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APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by lowering CD44+ and aldehyde dehydrogenase 1-positive stem cell populations, including ovarian tumors that are resistant to carboplatin. The ternary combination of APG-2449 with EGFR and mitogen-regulated extracellular signal-regulated kinase inhibitors overcomes osimertinib resistance in epidermal growth factor receptor-mutated NSCLC xenograft models. Conclusions APG-2449 provides potent and long-antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other drugs, according to our results. A phase 1 clinical trial has began to determine the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK + NSCLC refractory to earlier-generation ALK inhibitors. Clinical trial registration: CTR20190468 - Trial registration. gov registration of NCT03917043 and Chinese clinical trial registration: Clinical trial registration. gov.
Source link: https://doi.org/10.1186/s12885-022-09799-4
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