@Misspelly Haha, of course he likes the most technical. I'm sure he could put it together better. Thanks.
@JH888 Yes, but this is a fairly common phenomena for oncology. As a patient experiences more relapses, they become harder and harder to treat. You could definitely think about it like that, where water is resisting the firing of a piston - the more resistant a patient is, the more water there is blocking the spark and strength of fire.
Bisantrene acts through a completely new mechanism (FTO inhibition) to overcome this resistance, which is why it was so successful historically as a salvage treatment. While this is not the largest example, it certainly is one of the most potent when all factors are considered. Bisantrene achieves a CR in 3/4 patients who had recently failed (were resistant to) antimetabolite treatment.
Publications 40-years later reveal that FTO overexpression is a key driver of antimetabolite resistance, and Bisantrene is the most potent FTO inhibitor.
So, the answer to your question is yes, Bisantrene will work much better in combination with Doxorubicin in patients at earlier stages of their cancer journey. The combination should still demonstrate improvement over single-agent Doxorubicin, which is evidenced by the different mechanisms of action for each drug, Bisantrene's single agent efficacy, and the literature supporting the synergy between Doxorubicin and Bisantrene, with particular focus on FTO inhibition re-sensitizing resistant cancer cells to treatment. Other drugs used in combination improve efficacy by roughly 15-20%, so that's all Bisantrene needs to do while also providing cardioprotection.
@Boffin99
Bisantrene has also provided cardioprotection against the combination of Doxorubicin and Trastuzumab in vitro.
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