Medical

Scientists discover why a promising cancer drug failed in clinical trials – and how to fix it

Scientists discover why a prom...
Researchers have found out why a promising class of cancer drugs failed – and how to fix them
Researchers have found out why a promising class of cancer drugs failed – and how to fix them
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Researchers have found out why a promising class of cancer drugs failed – and how to fix them
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Researchers have found out why a promising class of cancer drugs failed – and how to fix them

As promising as some treatments are in lab tests, unfortunately they don't always meet hopes when translated to the real world. Now, scientists at Whitehead Institute for Biomedical Research have investigated a class of cancer drugs that failed in human trials, and found out why. Better yet, they went on to identify another drug that could finally make the treatment work.

Cancer cells are known to use all sorts of underhanded tricks to survive and spread in the body before the immune system can shut them down. To pull off all these extra processes, the crafty cells need to boost their protein production, which they do by ramping up activity in the proteasome. This system acts as a kind of recycling machine that breaks down old proteins into amino acids and rebuilds them as new proteins.

Realizing this, scientists developed drugs called proteasome inhibitors, which as the name suggests, disrupt that cellular machinery and prevent cancer from getting out of hand. Tests in the lab on cultured cancer cells proved effective, but frustratingly, when scientists tried to replicate that success in animal models and human patients, the cancer quickly developed resistance to the drugs.

The researchers on the new study set out to investigate why this might be the case. To do so, they explored the gene expression of thousands of tumors and hundreds of cancer cell lines, with a particular focus on those that have developed resistance to proteasome inhibitors. Ultimately the key seems to be related to how and where cancer cells are producing energy.

It turns out that these resistant cells have switched energy sources away from glucose and more towards the mitochondria, the powerhouse of the cell. The researchers confirmed that by manipulating the metabolism of cancer cells so they depended on the mitochondria – sure enough, these cells became immune to proteasome inhibitors.

From there, the researchers went on to discover that an existing anti-cancer molecule, named elesclomol, is effective against cancers that are immune to proteasome inhibitors. They found that this molecule binds to the gene FDX1, preventing the gene from encoding a vital enzyme in the mitochondria. Since these crafty cancers are now relying on the mitochondria, that makes elesclomol effective against them – although for some reason, the molecule needs to be bound to copper to work.

The research brings new hope to the fight against these particularly malicious tumors, and the team says the general principle – investigating changes in metabolism – could help unravel new treatments against other drug-resistant cancers.

The research was published in the journal Nature Chemical Biology.

Source: Whitehead Institute

3 comments
guzmanchinky
Almost nothing I can think of would relieve more pain and suffering than a cure for cancer...
akarp
With cancer drugs targeting various feeding systems of cancer cells, I would hope this gives us guidance to look at fasting as a useful tool. Oh, wait, can't patent that.
rederje
Our cells and life are 4 billions years of evolution as single cells struggling to be able to survive to anything and since only 0.560 bilion years life exists as multicellular organisms, and for this reason of old past memory, our cells are able to find numerous ways to survive to any complex products worked to kill them in cancers, because in cancers our cells, out of control, return to more than billion years back, in an intense fight to survive like in this very old past. For this elementary reason cancer is extremely difficult to cure with killing drugs over many years so that some cancer cells quickly develop resistance to any sophisticated complex drugs. It is better, before, to prevent and decrease the risk : no smoking, no alcool, no junk food, organic food, no too much sugar, endurance exercice every day, running sixty six stories easily, to make even in very old age like Robert Marchand cycling at 107 years old .... en.wikipedia.org/wiki/Robert_Marchand_(cyclist)