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am I correct in assuming that the peer review process is onerous...

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Boffin99

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26/04/24

15:01

Post #: 73526432
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Originally posted by RaceOncology: ↑

A very interesting paper which I have just had chance to read. A few comments on the paper.

Positives
It is absolutely fantastic for Race if the concept of anticancer cardioprotection is seen as a real possible in the pharma industry. The amount of scepticism we have encountered when talking to experts about bisantrene is huge as many doubt that it possible to have a drug that is an anticancer agent that protects from anthracycline cardiotoxicity. Having another team that has shown this is possible with a different approach is a huge advantage for us going forward.

I should add that you do great pharma deals when there is excitement about a sector, not solely off the back of good clinical data (both are best of course). This effect has been playing out in the radioactive theranostic space where great pharma deals are being done in recent times because the sector has suddenly become hot. To put it crudely, it is better to be hot than good. It is very hard to be hot when you are alone in an therapeutic area.

Negatives
The chemical used in this study (THZ1) is not really a drug, just a tool compound. It dates back over a decade and has not been advanced in the clinic. There are other CDK7 drugs in the clinic, but none have been studied for a cardioprotective effect. Adding to the issues around THZ1 is it appears to be quite a crude kinase inhibitor that also inhibits CDK12/13 and the anticancer activity seen may be due to an off-target effect (this is raised in the paper). This has relevance to the other more specific CDK7 drugs as there is no guarantee that what was seen with THZ1 will be seen with them.

The cardioprotection and anticancer activity seen with THZ1 is rather limited in scale. This is just an gut-feel opinion, but based on the data in the paper I would not be surprised if THZ1 didn't show much activity in human patients.

Finally I would add that CDK7 inhibitors as anticancer agents are limited to certain cancer types (i.e. CDK7 overexpressing cancers). Bisantrene is a much broader anticancer drug that basically works in any cancer that doxorubicin works. Even if a CDK7 inhibitor is advanced in the clinic, it is not going to displace bisantrene.

I would love to see a study combining a CDK7 inhibitor and bisantrene together with doxorubicin as this might be a very effective cardioprotective anticancer combination.

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am I correct in assuming that the peer review process is onerous and they can’t simply publish unsubstantiated claims?

I gather if the dual MOA can be easily explained then the scepticism may be less, such as in the article.

I would also be interested to know what the combo results of Dox + Dexrazoxane + Bisantrene look like. Or even just Dox + Dex v. Dox + Bis given Dex is already in the market as cardio protective (only).

Last edited by Boffin99: 26/04/24

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am I correct in assuming that the peer review process is onerous...

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