This
seems important for cancer, but also drug discovery in general, and molecular biology in general, and even science in general.
Do the dratted control experiments! They are tedious... and tell you that you are wrong.https://twitter.com/JSheltzer/status/1171850294910750721 …
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Replying to @Meaningness
So AFAIKT, this study shows that many cancer treatments in trial do not really treat the assumed mechanism of action. Can you help us understand (for people who don’t fully grasp this part of science) how it is that so many of these false positives arise?
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Replying to @krowney @Meaningness
Obviously, CRISPR based elimination of the underlying proposed genetic form of action shows that the original proposal for therapy is wrong. My question: these scientists who don’t use this control still had SOME basis of their conclusion. Why?
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Replying to @krowney
Presumably, they first found molecules that bound the target, then found that some of those also killed cancer cells, and assumed that they killed cancer cells *because* they bound the target. (Am on phone so can’t easily check whether OP gives an explanation.)
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Replying to @Meaningness
Thanks. Helpful. Am only an amateur on biochem and genetic engineering, so not all of the details are clear to me. So is it the case that an agent that “binds to a target” might do lots of damage to cells (cancerous and not) so that’s why these teams got false positives?
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Replying to @krowney
Yes from my vague memory of my quick skim of the paper it seems that these molecules are just generally toxic, for unrelated reasons, which makes them unsuitable as drugs obv
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Replying to @Meaningness
Right. Whence all the suffering of chemotherapy patients.
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Worse, even, I think. Those drugs are usually ones that selectively kill dividing cells (so any of your tissues that divide often are affected). These failures in preclinical probably just kill everything. (But again I didn’t read/remember paper carefully)
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