CRISPR genome editing eliminates head and neck tumours in 50 percent of experiments

Using CRISPR to edit a single gene in mice with head and neck cancer led to half of them becoming tumour-free.

The study, conducted by the group of Professor Dan Peer at the University of Tel Aviv, Israel, focused on a type of tumour called head and neck squamous cell carcinoma (HNSSC), the sixth most common tumour type, globally. The CRISPR system was used as 'molecular scissors' to inactivate the gene SOX2 in the DNA of the cells that make up HNSSCs.

'Theoretically, this approach could be effective against many types of cancer cells, and we are already working on additional cancer types, including myeloma, lymphoma, and liver cancer,' said Professor Peer.

The genetic causes of cancer can be linked to a group of genes called oncogenes, which usually regulate important cellular processes, such as mitosis or cell death. Generally, high activity of these genes is present in tumours, potentially due to acquired mutations.

Specific subsets of oncogenes that form a complicated 'pyramid' of molecular interactions are implicated in different types of tumours. Reducing the activity of these genes, through various approaches, has been proposed as one way to disrupt tumours and treat cancer.

SOX2 is an oncogene that has important roles in embryonic development and stem cells but is also frequently overexpressed in tumour cells across many different types of cancer. In HNSSC, SOX2 is known to be an important driver of tumour formation.

Publishing their findings in Advanced Science, the team tested whether inactivating SOX2 in HNSSC cells could be an effective treatment. They used an RNA-based formulation to deliver the CRISPR system to mouse cells. Crucially, the formulation was designed in a way that it should only interact with HNSSC cells and, therefore, not affect SOX2 in other cells.

Inactivating SOX2 in this way not only led to the disappearance of HNSSC tumours in half of the treated mice after 12 weeks, but also inhibited tumour growth and increased survival in 90 percent of them. These results challenge previous theories that editing one gene alone could be insufficient to treat cancer.

'Generally, CRISPR isn't used for cancer because the assumption is that knocking out one gene wouldn't collapse the pyramid,' said Professor Peer. 'In this study, we demonstrated that there are some genes without which a cancer cell cannot survive, making them excellent targets for CRISPR therapy.'

It remains to be seen how this approach would apply to other types of cancers that are less accessible, more difficult for CRISPR to penetrate due to their structure, have different genetics or are more difficult to selectively target. It is also unclear how this would translate to the clinic – many therapies that can cure cancer in mice prove ineffective in humans.

BioNews has recently covered multiple developments in cancer genetics (see BioNews 1247 and 1276) as well as CRISPR genome editing (see BioNews 1255).