Enzyme-Blocking Molecule Could Lead To Development Of Cancer-Fighting Wonder Drug

Chuck Bednar for redOrbit.com – Your Universe Online
Researchers at Imperial College London have identified a molecule that blocks the activity of a disease-causing enzyme – a breakthrough that could ultimately lead to the development of a wonder drug that could be used to fight cancer, neurodegenerative conditions such as Alzheimer’s disease, and even diabetes.
Writing in Friday’s edition of Nature Communications, lead investigator Ed Tate, a professor in the school’s department of chemistry, and his colleagues have discovered how to switch off N-myristoyltransferase (NMT), an enzyme that makes changes to proteins that has been “implicated in the development and progression of a range of human diseases.”
According Sarah Knapton, Science Correspondent with The Telegraph, the changes made by the NMT enzyme are irreversible and prevent damaged cells from dying. Instead, it actually speeds up their replication, which can cause cancer and can even make them resistant to chemotherapy, she said.
The enzyme has also been implicated in Alzheimer’s, epilepsy and inflammatory conditions.
In the new study, Tate and his colleagues analyzed living human cancer cells and located over 100 proteins modified by NMT, nearly all of which have been identified for the first time in their natural environment. They went on to map all of the proteins and establish a small drug-like molecule capable of blocking the enzyme’s activity – thus inhibiting its ability to modify the proteins, and leading to a potential new way to treat cancer and other NMT-related diseases.
“We now have a much fuller picture of how NMT operates, and more importantly how it can be inhibited, than ever before,” the professor said in a statement. “This is the first time that we have been able to look in molecular detail at how this potential drug target works within an entire living cancer cell, so this is a really exciting step forward for us.”
“This work opens a completely new avenue for the treatment of these diseases, and works very differently from other drugs currently under development,” he added, according to Knapton. “Eventually we hope this would simply be a pill you could take. It will be perhaps 10 years or so to a drug ‘on the market’ but there are many hurdles to get over.”
The researchers used a specialized set of tools to identify and analyze NMT and the proteins it changes, then used mass spectrometry to quantify the effect of an NMT inhibitor molecule. They utilized a process known as apoptosis, which programs a cell to die, to examine the interaction because the DNA that had been damaged.
The process, the study authors explained, is vital in cancer chemotherapy and is frequently deactivated in drug resistant cancers. Previous, scientists were only aware that NMT modified a handful of proteins during apoptosis. However, the results of the new study have led to the identification of several additional proteins types that are affected by the enzyme, suggesting potential new ways to help overcome drug resistance.
Experts from the University of York collaborated on the research, which was primarily funded by Cancer Research UK and The Biotechnology & Biological Sciences Research Council. Additional support was provided by The Medical Research Council, The Engineering and Physical Sciences Research Council, and the European Union.
“This promising research could lead to new treatments for cancer patients, and for people with other types of disease too,” Cancer Research UK senior science officer Dr. Emma Smith told The Telegraph. “Drugs targeting the molecule the team studied could make current cancer treatments more potent and help stop the cancer coming back. The next steps will be to develop this idea and make a drug – but there’s a way to go before we’ll know if it’s safe and effective in people.”