Hepatocellular carcinoma (HCC) in mice can be reduced via gene therapy, according to a study from the UC Davis Comprehensive Cancer Center (California, USA). This is achieved by inhibiting a specific protein, called galectin 1 (Gal1) that is frequently overexpressed in HCC. The research findings were released in Acta Pharmaceutica Sinica B.
Inhibiting galectin 1 (Gal1) is one target for hepatocellular carcinoma (HCC) treatment that this study looks at. Gal1 expression is very low in normal tissue and is thought to be a biomarker for HCC. On the one hand, Gal1 suppresses the immune system from attacking healthy tissue and on the other hand it has cancer-promoting roles, since it is overexpressed in HCC, both in human and mouse, promotes cancer growth, and keeps the immune system from attacking the tumor. Researchers discovered in this study that low survival rates and aggressive disease development in human HCC were linked to elevated Gal1 levels. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing. To silence Gal1, the researchers used a short interfering RNA (siRNA), called Igals1. The siRNA was packaged for delivery into adeno-associated virus (AAV) 9, with a preference to land in the liver. Igals1 successfully silenced Gal1 in the cancer and stroma, the surrounding supportive tissues, once it was within and around the tumor. The treatment effect of lgals1 siRNA was further explored by intersecting HCC at different time points of tumor load.
Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment, as indicated by comparing the spatial transcriptomic profiles of Gal1 silenced and OE HCC, as well as other parameters of developing tumors. Few researchers have explored using this approach against tumors.
Given that Gal1 is known to be overexpressed in a variety of cancer types, including lung, colon, and breast cancer, the authors believe that this study and other research show the promise of gene therapy for cancer treatments. Gal1 inhibition, however, might help human HCC patients. Moreover, the accumulation of this protein starts in diseased livers long before HCC develops. Gal1 inhibition may therefore be taken into consideration for the prevention of HCC.
Reference: Setayesh T, Hu Y, Vaziri F, et al. Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma. Acta Pharm Sin B. 2023. doi: 10.1016/j.apsb.2023.10.010