New drug shows possibility to suppress hard-to-treat cancers by targeting a hormone receptor
The drug has already shown to reduce the biomarkers of pancreatic cancer in lab studies. In mouse models, it has shown suppression of tumour growth and an increase in the life expectancy of the test mice
A group of researchers at the University of Sheffield, UK claim that they have invented a new anti-cancer drug that can be used to improve the quality of life and life expectancy of those suffering from hard to treat cancers including a relapsed breast cancer and pancreatic cancer.
The drug targets a hormone called adrenomedullin which promotes vasodilation (dilation of blood vessels) and decrease in blood pressure. Adrenomedullin also controls other processes in the body including kidney function, pregnancy and embryonic development. However, a site on this hormone also promotes tumour progression.
The findings of the study published in the journal ACS Pharmacology & Translational Science suggests that the drug is effective in treating pancreatic cancer in mice.
Double receptor sites
Adrenomedullin is important for various physiological processes in the body. Targeting it or stopping it from functioning to suppress tumour growth may not be viable as it would lead to high blood pressure.
However, the researchers found that adrenomedullin has two different receptor sites with which it can bind. Adrenomedullin-1 that controls blood pressure and adrenomedullin-2 that helps cancer cells communicate with each other and spread to nearby places.
Receptors are specific proteins on cells where a hormone can bind and exert its action. Specific hormones bind to specific receptor sites and not just any hormone can fit into any receptor site.
The new molecule that researchers have invented is an adrenomedullin-2 receptor antagonist, meaning it can compete with adrenomedullin to bind to the receptor site 2. The compound is so devised that it has a 1,000 fold higher selectivity to the receptor site 2 than for receptor site 1.
“We have designed a unique piece to fit into nature's jigsaw which will block signals from one receptor but allow the other to work as normal. In blocking the hormone’s communication with the cancer cells we are cutting off its supply to the things that it needs to thrive. This means tumours can’t grow as fast as they are starved of the resources they need and it becomes more difficult for them to spread to other areas of the body,” said Dr Tim Skerry, corresponding author of the study and a professor of orthopaedic biology at the Department of Oncology and Metabolism, University of Sheffield, in a news release.
A long journey
Dr Skerry and his team have been working on this project for the past 12 years. The drug has already shown to reduce the biomarkers of pancreatic cancer in lab studies. In mouse models, it has shown suppression of tumour growth and an increase in the life expectancy of the test mice.
The team has already found a spin-out company Modulus Oncology to fast track the clinical trials of the drug within two years.
As per the news release by the University of Sheffield, pancreatic cancers are highly aggressive and hence have the lowest survival rates in all the common types of cancer — the 5-year survival rate is only 7 percent. Due to the nature and location of the cancer, it can easily spread to the liver and stomach and not much can be done to treat it in time.
Their study, if it gives good results in clinical trials, would hence lead to a new class of anticancer drugs along with a better understanding of adrenomedullin receptors.
For more information, read our article on Pancreatic cancer
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