Render of a DNA helix

New drug target identified for colorectal cancer

Around 15% of colorectal cancers are resistant to standard therapies but ‘switching off’ a specific gene could offer new avenues for treatment

A potential drug target for colorectal cancer has been discovered that could help to treat around 15% of cases.

The target, which was found as part of the DepMap project, could help to treat types of cancer that are resistant to standard therapies, opening up new options for patients when conventional approaches prove ineffective.

Understanding dependencies, exploiting weaknesses

Many mutations that are essential for cancer cell growth rely on specific cellular processes and gene products. These relationships between a cancer-causing mutation and other gene products are called dependencies.

Developing new targeted therapies relies on finding and understanding these mutations, as well as their dependencies, in order to find weaknesses and take advantage of them.

Identifying weaknesses is not always straightforward, however, as cancer genomes can be incredibly diverse and may present with completely different molecular targets, even in the same type of cancer.

In many cases, the relationships between the mutations present in cancer cells and the effects on the cells are unclear, but work is ongoing to help understand them better.

Mapping the course

The Cancer Dependency Map (DepMap) project, a collaboration between the Wellcome Sanger Institute and the Broad Institute, aims to catalogue genetic dependencies and find biomarkers that can be used to predict them.

To do this, researchers profile hundreds of cancer cell lines for genomic information and their sensitivity to having different molecular pathways disrupted.

The project’s online portal empowers researchers to make discoveries by making datasets freely available and providing user-friendly analytical and visualisation tools.

The new target

DepMap has newly identified one gene, WRN, as a potential target in cancer cells with microsatellite instability, a condition where cells lose the ability to recognise and fix the small errors that commonly occur during DNA replication.

Around 15% of colorectal cancers are associated with microsatellite instability and are known to be resistant to some standard therapies.

Research recently published in Cancer Discovery used ‘mini organ’ models grown from cancer cell lines with an inactive WRN gene. The researchers were able to show that cell lines resistant to chemotherapy, immunotherapy and existing targeted therapies all required WRN to survive. Inhibiting WRN in colorectal cancer could therefore be a new target for treatment.

“Understanding the weaknesses in cancers to help make precision medicine is the goal of the Cancer Dependency Map. This study has reinforced WRN as a target for drug development in colorectal cancer, with the possibility of it also being important in other cancers that show microsatellite instability,” said Wellcome Sanger Institute group leader, Dr Mathew Garnett.

He added: “If these drugs can be developed and are shown to be successful, it would offer a new therapy to people whose cancer has become resistant to existing treatments.”

Please note: This article is for informational or educational purposes, and does not substitute professional medical advice.