Publication highlights

Researchers at the Crick investigated whether dendritic cells detect dead cancer cells via a receptor called DNGR-1, which detects F-actin. Looking at mice with and without the DNGR-1 receptor that had been exposed to carcinogens, they found that mice without DNGR-1 developed tumours significantly earlier and to a greater extent. Next, the team examined whether certain cancer mutations were more likely to be found in the tumours of mice without DNGR-1. They reported an increase in mutations in proteins that bind to the F-actin scaffold. This may be because, in mice with DNGR-1, mutations in these proteins are highlighted as a red flag for the immune system. Without DNGR-1, there's less evolutionary pressure for cancer cells to get rid of them.

Researchers at the Crick have shown that over 40% of variation in kidney cancer behaviour is due to non-genetic factors. The team analysed the DNA and RNA of 243 samples from 79 people with kidney cancer in the TRACERx Renal study, to understand both genetic and transcriptional variation (when the genes are read in the cell and converted into proteins). They showed that over 40% of transcriptional variation could not be accounted for by major cancer mutations in the DNA. Instead, it was happening when the DNA was being read in the cells and converted into proteins. Their research identified four types of transcriptional variation which give tumours an advantage, which could be targeted by new treatments or help doctors understand the risk of a person’s cancer spreading.

Researchers at the Francis Crick Institute have mapped all the possible outcomes of changes to a tumour-suppressing gene called VHL. They used a new method called saturation genome editing to track the function of over 2,000 different VHL variants in human cells over time, finding that most variants did not impact the survival of the cells, suggesting that people with these variants may not have a significantly higher risk. Other variants were shown to be faulty and caused the cells to die, suggesting people with these variants could be monitored for cancer risk. This could also identify people with VHL mutations who would benefit from certain drugs like belzutifan.

An important aspect of cancer research is the model systems that researchers use to test new therapies. Within the TRACERx lung cancer study, researchers from the CRUK Lung Cancer Centre of Excellence have performed a direct comparison of patient tumours and a commonly used laboratory model - ‘patient-derived xenograft’ or ‘PDX’ models - in which patient tumour tissue isgrown within immunocompromised mice.

The researchers found that patient tumours are often genetically complex, with many co-existing subclones (groups of cell populations with different characteristics). However, the PDX models often only represented one of these subclones. This over-simplicity of PDX models might limit their ability to predict patient responses. These findings will shape the future use of PDX models in lung cancer research and clinical studies.

Asymptomatic PCR testing for NHS staff, provided by the Francis Crick Institute and University College London Hospitals (UCLH) NHS Foundation Trust and its diagnostic partner Health Services Laboratories, effectively detected COVID-19 infections that would have otherwise been missed. The researchers examined test positivity rates across different NHS trusts, observing that from the 680,000 tests run through the testing pipeline, 40.8% of all positive tests were from UCLH and The Royal Marsden NHS Foundation Trust. This high incidence suggests a significant number of additional infections were being detected by this strategy.

Researchers from the Bates, Turajlic and Sahai labs have collaborated to develop a computer model to analyse how the way in which tumours grow affects their genetic makeup. Using this new model, they have identified links between tumour growth and shape, and how quickly a patient’s cancer might progress.