Genetic Engineering Publications - GEG Tech top picks

One of the biggest challenges facing cancer researchers is understanding why some patients do not respond to treatment. In some cases, tumours have what is known as multi-drug resistance (MDR), which severely limits treatment options for patients. However, researchers have discovered one of the causes of MDR and a potential strategy to combat it. In their study, the researchers began by using CRISPR technology in mouse stem cells to search for mutations that generate resistance to antitumor agents such as cisplatin, rigosertib or ultraviolet light. Mutations in the FBXW7 gene appeared early on, suggesting that this mutation could confer MDR. In addition, FBXW7-deficient cells showed an excess of mitochondrial proteins, which has already been shown to be associated with drug resistance. Nevertheless, a detailed analysis of these organelles further revealed that the mitochondria of these multi-drug resistant cells appeared to be under severe stress. Finally, the researchers showed that the antibiotic tigecycline is toxic to FBXW7-deficient cells because it activates the 'integrated stress response'. This study thus opens a new avenue of research to combat multidrug resistance.

A group of researchers set out to identify the genes that play a role in immunotherapy resistance. In today's cover story in Cell Reports Medicine, they describe an important factor behind this resistance to therapy and a potential way to counter it. The researchers grew tumour cells in their laboratory and inactivated one gene per cell at a time using the CRISPR/Cas9 technique. Then they treated the tumour cells with T cells or NK cells to analyse which genes were involved in resistance against the immune cells. This led to the discovery of three genes from the same family. The screening led us to an entire gene family, which is a real success. Indeed, when they switched off these genes including RNF31, the tumour cells were destroyed much more efficiently by T cells and NK cells. In addition, they found that inhibiting RNF31 also increased the sensitivity of T cells to tumour cells that were invisible on the surface of immune cells. This so-called bystander effect may amplify the effect of the treatment.