Drugging the “undruggable”

A research project we funded in 2013 allowed Dr Laura Soucek to develop a new treatment she was working on, proving that it was ready for clinical trials. The treatment, called Omomyc, works by attacking a protein in cancer cells called MYC and shutting down the cells ability to grow and divide. For decades, people had been saying this approach to treating cancer was impossible. Some even called MYC the "undruggable" target in cancer. Defying the sceptics, and beating the odds, Laura's perseverance paid off and the first patients were treated with Omomyc on clinical trials that started in 2021.

There is a molecule in our cells that drives tumour growth in 70% of all cancers. It’s called MYC, and for decades scientists have been searching for a way to develop drugs that could treat a wide range of cancers by targeting this molecule. But for a long time, achieving this seemed impossible.

MYC is a protein that exists deep within the cell, at its very core – the nucleus – and has the kind of shape that makes it difficult to target with drugs. Because MYC is central to so many different mechanisms within the cell, scientists also feared that blocking it might cause catastrophic side effects. Researchers referred to MYC as ‘drugging the undruggable’.

But where most saw insurmountable challenges and difficulties, some saw a huge opportunity. Dr Laura Soucek, a cancer researcher based at the Vall d'Hebron Institute of Oncology in Spain, has dedicated her career to solving the MYC problem.

I must admit that, back then, I didn’t even take the risk itself into consideration. In my mind, targeting MYC was a great opportunity for cancer treatment, and the fact that nobody had done it before made it even more appealing and important to try.

Rising to the challenge

In the early 2000s Laura Soucek, then a PhD student in Rome, decided to challenge the dogma of “undruggability” that existed around MYC. Her early research led to the development of a treatment, called Omomyc, that she was confident would be able to target and inactivate MYC, preventing cancer cells from dividing. Referring to these early experiments, Dr Soucek said, “We were able to show that Omomyc has a dramatic impact on cancer cells, and only mild, well-tolerated and completely reversible side effects on normal tissues.”

Emboldened by these promising results, Laura packed her bags and moved to San Francisco for a 1-year fellowship, in which she hoped to further test Omomyc as a cancer treatment. One year turned into 10 and it became clear that Omomyc held real promise as a potential treatment. Another move brought Laura to the Vall d’Hebron Institute of Oncology in Barcelona, where she was able to show that Omomyc could shrink tumours grown from human cancer cells in mice – the gold standard for determining if a drug has the potential to go on to clinical trials in people.

These results were exciting, but there was one important problem – all these studies used Omomyc in a form of treatment called gene therapy. And while gene therapy is a promising and exciting area of research, it’s not something that can be done in patients yet.

How is MYC linked to cancer?

What is MYC and how is it linked to cancer?

In healthy cells, MYC plays an important role in how our cells divide and grow. When a cell needs to divide, it starts producing the MYC molecule. The problem arises when the cell can’t switch off production of MYC, sending constant signals telling the cell to multiply. This can lead to uncontrolled cell division and the development of cancer.

In 1991, researchers showed that the MYC molecule was something called a transcription factor. Transcription factors act as molecular switches that can turn on genes that also stimulate cell division, causing a snowball effect of more and more cellular growth and division. This is what makes MYC such a great potential target for cancer treatment. If we can somehow block MYC and stop it from initiating cell division, it would put a brake on the runaway growth and division of cancer cells.

Over time, researchers identified more and more cancers that seemed to be driven by cancer cells producing high levels of MYC, cementing its status as a highly desirable treatment target for a wide range of cancers.

Taking a chance

Laura was told it would be impossible to shift Omomyc from a gene therapy to a drug. They said the drug would be too bulky, it wouldn’t be able to get into the cell, never mind the nucleus, where it could stop MYC from making cancer cells divide. Undeterred by the sceptics, Laura Soucek set out to turn her idea into a reality. Her team did the research that turned Omomyc from a gene therapy into a drug molecule and showed that it could enter the nucleus and attack MYC deep within the cell. Driven by this success, in 2013 Laura founded Peptomyc, a company that could attract investors to help develop Omomyc into a clinical drug as quickly as possible.

Laura wasn’t the only one willing to take a chance on what others considered an impossible challenge. Thanks to the generosity of supporters like you, in 2013, Worldwide Cancer Research was able to fund a 3-year project led by Laura to give her idea the push it needed towards becoming a potential new cancer treatment.

We had some hints that Omomyc could be developed into a drug, but it was clearly still a high-risk project, which required a funding agency brave enough to believe in us and the potential rewards. Worldwide Cancer Research was exactly that - they recognised the value and potential of what we were doing and provided us the resources we needed for our project to take off. We will always be grateful for that.

Backing for clinical trials

During her project Laura continued to discover more about Omomyc and how it worked by testing it in lung cancer cells and mice – putting them in an ideal position to take Omomyc into clinical trials. The project delivered the proof of principle that Omomyc represented a promising new treatment strategy for lung cancer, as well as potentially many other types of cancer. Laura said: “[Worldwide Cancer Research] offered us the resources to produce important preliminary data, which eventually were the bases for other prestigious international grant applications (such as the ERC consolidator grant by the European Research Council) that supported our project after that”.

That research is now heading towards having a real benefit for cancer patients. In 2019, Laura was awarded 2 million Euros from the EU Horizon 2020 Research and Innovation programme to take Omomyc into clinical trials, which started in 2021 and will recruit patients with lung, breast and bowel cancer. But that’s not all. If successful, Omomyc has the potential to be used in many types of cancer and the approach Laura used to “drug the undruggable” could be extended to other treatment targets that have been considered impossible to reach.

Because we took a chance on Laura’s research all those years ago, we are now on the verge of an innovative new treatment that could benefit cancer patients across the world very soon. We couldn’t have done it without you.

Breakthroughs like Dr Laura Soucek's are only possible because of your kindness and generosity. Your support backs scientists like Laura to pursue their idea and make a start on finding new cures for cancer.