ICR discovery could lead to new series of cancer drugs

Researchers at the Institute of Cancer Research (ICR) in London have discovered new inhibitors that block the action of a protein involved in driving several cancer types.

According to the team, with further research, the compounds could be developed into drugs to treat a range of cancers.

Initially discovered as a cancer-driving protein in B-cell lymphoma, B-cell lymphoma 6 (BCL6) has since been linked with an increasing number of blood cancers and solid tumours, including some forms of leukaemia, breast cancer and non-small cell lung cancer.

The protein works by binding to hundreds of target genes, before switching them off by recruiting several different ‘co-repressor’ proteins.

In the new study, published in the journal Scientific Reports, the team from the Centre for Cancer Drug Discovery at the ICR describe an integrated workflow that led to the discovery of the novel inhibitors of the BCL6 protein.

The researchers used a combination of high throughput screening, multiple biophysical techniques, X-ray crystallography and cell-based methods to discover the novel compounds offering the potential to block the ability of BCL6 to switch off its target genes and kill cancer cells.

“Identifying drug compounds that disrupt protein-protein interactions, such as the BCL6-corepressor interaction, has traditionally proved to be extremely challenging,” explained study leader Dr Rob van Montfort, who leads the Hit Discovery and Structural Design Team at the ICR, saying that the combination method used by the team meant they were able to “effectively discover several BCL inhibitors from multiple chemical series”.

“It’s exciting to reach this stage, creating a shortlist of promising compounds and helping to improve them to the very potent and selective inhibitors we have published previously and that have the potential to move into the next phase of drug discovery,” he added.

In November 2022, researchers from the ICR and the Royal Marsden NHS Foundation Trust revealed joint plans to create a new generation of treatments that target the ecosystems within the body supporting cancer.

The five-year strategy aims to accelerate progress for cancer patients by leveraging the latest advances in scientific knowledge and technology to focus research on the cells, signals and immune responses in the tissue environment that nurtures tumours.

The researchers will also employ artificial intelligence to design new ways to combine existing treatments and smart dosing strategies, with the aim of doubling the survival of patients with advanced cancer within a decade.