Genetic Engineering Publications - GEG Tech top picks

Breast cancer is the second most common cancer in American women, and triple-negative breast cancer (TNBC) is a more aggressive and deadly form of the disease that accounts for 10-15% of all breast tumors. Using a comprehensive, state-of-the-art genomic screening method known as CRISPR/CAS9 screening, scientists were able to identify a specific enzyme called UBA1 that proved to be an ideal therapeutic target. Using a new UBA inhibitor drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice. Previous research has shown that UBA1 inhibitors can have a positive impact on hematological cancers such as acute myeloid leukemia and chronic myeloid leukemia. This study, recently published in PNAS Nexus, is the first to suggest that UBA1 inhibitors may be effective in TNBC. TAK-243 was recently tested in early phase trials, paving the way for potential testing in TNBC patients. The researchers also determined that the c-MYC gene can be harnessed to cooperate with TAK-243 to initiate a cellular stress response and improve the drug's ability to combat TNBC. This supports the idea that TAK-243 may be effective in TNBC with high c-MYC expression, where c-MYC may serve as a biomarker for drug response.

An innovative combination therapy can force malignant breast cancer cells to turn into fat cells. This can be used to prevent the formation of metastases in mice, as researchers at the University of Basel’s Department of Biomedicine recently reported in the journal Cancer Cell.

CAR T cell immunotherapies are more effective as a treatment for patients with leukemia or B cell lymphomas because once they are re-injected into the patient, they migrate and lodge in the bone marrow and other organs that make up the lymphatic system. However, for solid tumours, such as breast cancer, the CAR T cells have difficulty migrating to the tumour because of the microenvironment that surrounds it. Recently, a study conducted by researchers at the UNC Lineberger Comprehensive Cancer Center, shows that adding a small molecule to the CAR T cell-based treatment could stimulate the Th17 and Tc17 cells of the immune system to effectively attack solid tumours. To stimulate the accumulation of these Th17 and Tc17 cells in the vicinity of solid tumours, the research team discovered that the stimulator of interferon agonist (STING) genes, cGAMP, activates the human STING and is known to stimulate the human immune system. The various experiments showed that mice injected with cGAMP showed increased proliferation of T cells and these cells migrated to the tumour site. The end result was a significant decrease in tumour growth and improved survival.  

In this study, the scientists used a transposon mutagenesis strategy based on a two-step sleeping beauty (SB) forward genetic screen to identify and validate new tumor suppressors (TS) in this disease. They generated 120 siRNAs targeting 40 SB-identified candidate breast cancer TS genes and used them to downregulate expression of these genes in four human TNBC cell lines. Their validation of several new TS genes in TNBC demonstrate the utility of two-step forward genetic screens in mice and offer an invaluable tool to identify novel candidate therapeutic pathways and