@ma420
Bisanthrene PLUS Radiation therapy: Would it work?
[CAUTION - FACTS plus a lot of SPECULATION]
The trend in cancer therapy is towards combination treatments, so that would not be a wrong direction to take. Side effects can limit that - so those need to be kept in mind.
The idea with combos includes strategies to break the DNA, and then also overwhelm cancer cells' DNA repair mechanisms. Combinations do that better than monotherapies. That also seems to help avoid resistance - which can develop particularly with combos. In that sense, the "what doesn't kill me makes me stronger", applies to cancer cells as well as bacteria!
In theory - most definitely, YES. In the lab, its a YES too! Below is an abstract on some lab work showing there was additive effect.
In the absence of much research using Bisantrene (in combo with radiation), we can learn some lessons from Doxo (same class)! There are limits to any learning, of course - but I will try!
Doxorubicin is already used with radiation therapy to treat Lymphomas, but cardiotoxicity limits the amount and even how its used! In cancers where the chest (anywhere near the heart) needs irradiating (Lymphomas, Left breast cancer), Doxo + Radiation have additive heart damaging effects! You want additive cancer killing, not literal heart breaks multiplied > 1.0. As it happens, Doxorubicin is also known to have radiosensitizing effects - making radiation killing more powerful. That's what you want!
Whats interestingly for RAC, is that the MOA that leads to radiosensitizing effects (arresting cells in the so called G2/M phase of replication), is also shared with Bisantrene! So, we can expect Bisantrene to have radiosensitizing effects!
If it works that way, Bisantrene earns a place in the treatment combo regimes that feature Doxorubicin, again! The great thing here is the possibility that, even in diseases where monotherapy Bisantrene is known to be inferior to monotherapy Doxorubicin, the Bisantrene-Rradiation combo only needs to be non inferior to the Doxo-Radiation combo, in order to achieve better overall survival as well as better Quality of Life - via better hear health.
AT (at Clarity) was talking about approaches using Immuno Oncology and radiation combo - there is evidence from Paul Donnely's lab - in small cell lung cancer. The success with Enzalutamide is another example of combos with radiation (ENZA upregulates PSMA receptors, making PSMA prostate cancer more sensitive to PSMA targeting radiation therapies).
Telix is trialing its radiation drug TLX591 on top of SOC (ARPI's or Doxataxel). TLX591 (previously called huJ591), is an old drug whose development stalled probably due to side effects (it did have lots of them). Having failed to make it on its on, its coming back in as an additional drug - in combo with ARPI's and Taxanes.
The age of monotherapy in cancer is in the rearview mirror! Provided side effects can be managed!
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Sorry for the long read/write up - and apologies if its a bit mixed up! Friday!
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