Thanks for the great recap, some of this looks very promising! I remember reading your personal blog several years back, you (and James Watson) were both optimistic about the possibility of leveraging the Warburg effect in cancer therapies. Why didn’t much progress happen on that front? Is it that we haven’t invested the necessary resources there and instead got excited by alternative promising directions? Or did we come to learn of new information that reduced the feasibility of that strategy?
And another thought, it seems like there is some need for rapid experimentation on voluntary patients to optimize protocols (e.g. how many days to fast, whether to do oncolytic virus therapy and immune checkpoint inhibitors together etc.), and the risk-averse hyper-bureacratization around clinical trial protocols seems like a huge impediment to progress for cancer specifically.
It’s not a true “pan-cancer” phenomenon; the distribution of % of ATP due to glycolysis, across cancer cell lines, overlaps heavily with the same distribution for non-cancerous cells, i.e. you can’t effectively distinguish cancer from non-cancer by its glycolysis activity. Also, not all glycolysis-using cancers will actually die if you block glycolysis; some of them just adapt/evolve to use cellular respiration instead.
So, glycolysis-inhibition drugs can, at best, be effective against the fraction of cancers that are truly obligate glycolysis-dependent...and even there, they’ll be side-effect-heavy like conventional chemotherapy, since they’ll also target glycolysis-dependent healthy cells (which are not rare!) In other words, even if a glycolysis inhibitor turns out to be effective against some cancers, it’s not going to be anywhere near universally applicable.
The glycolysis-inhibitor drug candidate I used to be excited about was 3-bromopyruvate, which indeed was reported to eradicate some big tumors in rats and turned very advanced liver cancer necrotic in a human case study.
The lead researcher, Young H. Ko, has since left Johns Hopkins—she sued them in 2005 for race and gender discrimination after her contract was not renewed, but lost the case. She’s now founded her own company, KoDiscovery (the website is pretty scammy-looking but I’m trying to suspend judgment) and has registered their first clinical trial with the FDA, currently ongoing in Korea.
Unfortunately a German alternative-medicine clinic is under investigation for manslaughter when three patients died after being administered the compound. (The article isn’t claiming the clinic is at all affiliated with Ko or her company.)
The phase I/II trial is set to complete next year, so we’ll have more information then.
Thanks for the great recap, some of this looks very promising! I remember reading your personal blog several years back, you (and James Watson) were both optimistic about the possibility of leveraging the Warburg effect in cancer therapies. Why didn’t much progress happen on that front? Is it that we haven’t invested the necessary resources there and instead got excited by alternative promising directions? Or did we come to learn of new information that reduced the feasibility of that strategy?
And another thought, it seems like there is some need for rapid experimentation on voluntary patients to optimize protocols (e.g. how many days to fast, whether to do oncolytic virus therapy and immune checkpoint inhibitors together etc.), and the risk-averse hyper-bureacratization around clinical trial protocols seems like a huge impediment to progress for cancer specifically.
ah. I’m now pretty bearish on Warburg. https://roamresearch.com/#/app/srcpublic/page/fBd011iWS
It’s not a true “pan-cancer” phenomenon; the distribution of % of ATP due to glycolysis, across cancer cell lines, overlaps heavily with the same distribution for non-cancerous cells, i.e. you can’t effectively distinguish cancer from non-cancer by its glycolysis activity. Also, not all glycolysis-using cancers will actually die if you block glycolysis; some of them just adapt/evolve to use cellular respiration instead.
So, glycolysis-inhibition drugs can, at best, be effective against the fraction of cancers that are truly obligate glycolysis-dependent...and even there, they’ll be side-effect-heavy like conventional chemotherapy, since they’ll also target glycolysis-dependent healthy cells (which are not rare!) In other words, even if a glycolysis inhibitor turns out to be effective against some cancers, it’s not going to be anywhere near universally applicable.
The glycolysis-inhibitor drug candidate I used to be excited about was 3-bromopyruvate, which indeed was reported to eradicate some big tumors in rats and turned very advanced liver cancer necrotic in a human case study.
The lead researcher, Young H. Ko, has since left Johns Hopkins—she sued them in 2005 for race and gender discrimination after her contract was not renewed, but lost the case. She’s now founded her own company, KoDiscovery (the website is pretty scammy-looking but I’m trying to suspend judgment) and has registered their first clinical trial with the FDA, currently ongoing in Korea.
Unfortunately a German alternative-medicine clinic is under investigation for manslaughter when three patients died after being administered the compound. (The article isn’t claiming the clinic is at all affiliated with Ko or her company.)
The phase I/II trial is set to complete next year, so we’ll have more information then.