Novel medication could improve future and quality for patients with difficult to-treat malignant growths

Novel medication could improve future and quality for patients with difficult to-treat malignant growths


  • Post By : Kumar Jeetendra

  • Source: University of Sheffield

  • Date: 09 Sep,2020

The Sheffield researchers founded the spin-out Modulus Oncology with a group of experienced biotech entrepreneurs to fast-track the drug into clinical testing over two decades.

The researchers founded the spin-out firm Modulus Oncology, along with a team of seasoned biotech entrepreneurs, to fast-track the drug into clinical testing over two years.

The Sheffield team made the discovery after analyzing a hormone, called adrenomedullin, which controls blood pressure and other vital body processes, but also stimulates the growth and spread of cancer.

Using novel drug molecules, called adrenomedullin-2 receptor antagonists, the scientists found a way to block the way that adrenomedullin is used in communicating with cancer cells, without affecting the way it can help to regulate vital processes in the body such as blood pressure.

Findings of this pioneering study, published in the journal ACS Pharmacology & Translational Science, show the new drug molecules have a beneficial effect in treating pancreatic cancer in mouse models.

Pancreatic cancer has the lowest survival rate of all common cancers, with just seven per cent of patients surviving five-years after diagnosis.

Professor Tim Skerry in the University of Sheffield’s Department of Oncology and Metabolism and a team of academic and industrial scientists from a variety of scientific disciplines have been focusing on the groundbreaking research for the last 12 years.

The most extraordinary part of this new therapy is the fact that nature designed the hormone adrenomedullin to have two different types of receptor – one which helps to regulate our blood pressure and the other which is involved in the way that cancer cells communicate with each other and the host cells, helping cancers to grow and spread.”Professor Tim Skerry, University of Sheffield

“We’ve designed a unique piece to fit into nature’s jigsaw which will block signals from 1 receptor but allow another to work as normal. In blocking the hormone communicating with the cancer cells we’re cutting off its source to what it needs to thrive. This implies tumours can’t grow as fast as they’re starved of the resources that they need and it becomes more difficult for them to spread to other regions of the body.

He added:”Pancreatic cancer tumors are notoriously competitive and difficult to deal with and their place makes it effortless for the cancer to spread to nearby organs such as the liver and gut. The character of pancreatic cancers means it is really hard to get current drugs into the tumor. We believe adrenomedullin-2 receptors offer benefits for pancreatic cancer patients.

“Over the past 30 years the diagnosis and treatment of the vast majority of cancers has evolved rapidly, helping people survive the disease than previously. But, advances in treating pancreatic cancer and enhancing patient outcomes have had little impact on life expectancy. There continue to be cancers that are resistant to treatment and research is required to solve those problems.”

The novel drug molecules were found to be effective in treating pancreatic cancer tumours in mice models. Tumours did not grow as fast which offers evidence to suggest life expectancy could be extended. The compound is different from traditional therapies like cytotoxic drugs and radiotherapy because it targets a very few of cells and does not harm healthy cells in the body. It’s hoped this will improve quality of life for patients undergoing therapy.

It is thought the concept is also beneficial in other classic hard-to-treat cancers like relapsed breast cancer and lung cancer.

Building on more than a decade of research, and with significant grant funding from The Wellcome Trust, the scientists created the spin-out company Modulus Oncology along with a group of biotech entrepreneurs.

Dr Alan Wise, CEO of Modulus Oncology, said:”The team at the University of Sheffield have performed a few genuinely pioneering research here and I am delighted to be helping Modulus Oncology take this very important work towards clinical testing. Our goal is to demonstrate benefit for cancer patients in addition to developing a successful UK biotech company.”

Modulus Oncology is now in talks with a number of life science investors to boost funds for first-in-human clinical trials designed to generate powerful clinical proof of concept data.

Journal reference:

Avgoustou, P., et al. (2020) Discovery of a First-in-Class Potent Small Molecule Antagonist against the Adrenomedullin-2 Receptor. ACS Pharmacology & Translational Science.

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