Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in breast and ovarian cancer
Year: 2024
Type: article
Abstract: The poor vascularization of solid tumors results in oxygen-deprived areas within the tumor mass. This phenomenon is defined as tumor hypoxia and is considered to be a major contributor to tumor progression in breast and ovarian cancers due to hypoxia-cascade-promoted increased metastasizing capacity. Hence, targeting hypoxia is a strategic cancer treatment approach, however, the hypoxia-modulating drugs face several limitations in monotherapies. Here, we investigated the impact of the potent hypoxia-inducible factor inhibitory compound acriflavine on tumor cell proliferation, migration, and metabolism under hypoxic conditions. We identified that acriflavine inhibited the proliferation of breast and ovarian tumor cells. To model the potential benefits of additional hypoxia response inhibition next to standard chemotherapy, we combined acriflavine with a frequently used chemotherapeutic agent, paclitaxel. In most breast and ovarian cancer cell lines used, we identified additive effects between the two drugs. The most significant findings were detected in triple-negative breast cancer cell lines, where we observed synergism. The drug combination effectively impeded tumor growth and metastasis formation in an in vivo orthotopic triple-negative breast cancer model as well. Additionally, we demonstrated that an epithelial-mesenchymal transition inhibitory drug, rolipram, combined with acriflavine and paclitaxel, notably reduced the motility of hypoxic triple-negative breast cancer cells. In conclusion, we identified novel drug combinations that can potentially combat triple-negative breast cancer by inhibiting hypoxia signaling and hindering cell migration and metastasis formation.
Source: Biomedicine & Pharmacotherapy
Institutions: Semmelweis University, National Institute of Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,420
Awards: G1178045599, G6678201728
OpenAlex ID: W4403942758