Dr Konstantinos Tzelepis was awarded a Leukaemia UK research fellowship in 2020. Our fellowships provide vital funding at a critical point to enable early career researchers with a passion for science, a desire to develop new ideas and translate scientific advances into clinical practice, to become established independent researchers and the leading blood cancer scientists of tomorrow.

Thanks to our support, Kostantinos’ research has led to the development of a new class of cancer drug with the potential to treat leukaemia.

"This is the beginning of a new era for cancer therapeutics." - Dr Konstantinos Tzelepis

In a study published in 2017, a collaborative effort between the Gurdon Institute at the University of Cambridge and the Wellcome Sanger Institute, showed how one such enzyme, METTL3, plays a key role in the development and maintenance of acute myeloid leukaemia. The enzyme becomes over-expressed – that is, over-produced – in certain cell types, leading to the disease.

This drug has been developed to treat Acute Myeloid Leukaemia (AML). AML is a cancer of the blood in which bone marrow produces abnormal white blood cells known as myeloid cells, which normally protect the body against infection and against the spread of tissue damage. AML proceeds rapidly and aggressively, usually requiring immediate treatment, and affects both children and adults. Around 3,100 people are diagnosed with the condition every year in the UK, the majority of whom are over 65 years of age.

Now, Professor Kouzarides, Dr Tzelepis and colleagues at the Wellcome Sanger Institute and STORM Therapeutics, have identified a potential drug, STM2457, that can inhibit the action of METTL3.

We spoke to Konstantinos about this break-through:

"This is the result of many years of research. And in this study we're particularly focused on developing a drug that is inhibiting a protein called METTL3. METTL3 is an enzyme that we found that is overrepresented in a leukaemia cells versus normal.

METTL3 is a protein that we all have in our body, in most of the cells of our body, if not all of the cells. But in some of the cancers including AML, acute myeloid leukaemia, the cancerous cells, the leukaemia cells in particular, they actually have higher levels of this protein.

And this is how we prioritize this target compared to other targets that we have from the same protein family. And it actually paid off because we saw that under a certain level of blocking of this protein, this is devastating for the cancer cells, however, for the normal cells and especially for the STEM cells, as we show in the current study, the loss of this protein was, or the function of the protein was dispensable."

The next step for this drug is to enter clinical trials in 2022 with the first cohort of patients being adults diagnosed with AML who have not responded to current treatment i.e. chemotherapy. If the results are as expected, then this will then be extended to children with AML.

Fiona Hazell, Leukaemia UK CEO said, "We are delighted to be a part of this ground-breaking research. Not only has it established a new way of identifying potential drug targets, developing targeted treatments to select and destroy cancer cells but ultimately, could make a real difference to the lives of patients with AML.

Around 3,100 people each year are diagnosed with AML in the UK and treatments haven’t progressed for the past 30 years, so this research brings hope that patients diagnosed with AML will have more treatment options in the future.

We fund early career researchers for this exact reason, they have new, exciting ideas that translate scientific advances into clinical practice, giving patients hope and developing new treatments in our fight against blood cancer.”

The research was supported by Cancer Research UK, the European Research Council, Wellcome, the Kay Kendall Leukaemia Fund, and Leukaemia UK.

Read the media release from the University of Cambridge

Read more about Konstantinos Tzelepis and his research