Nearly everyone knows someone with cancer. There’s a lot of awareness around cancers of the breast and lung, but liver cancer (hepatocellular carcinoma) doesn’t see much airtime. Despite its lack of fame, hepatocellular carcinoma is the fifth most common cancer in the world, and was responsible for 695,000 deaths in 2008 alone. Liver cancer is aggressive. Five years after diagnosis, the relative survival rate is only 14%, largely because we just don’t know how to treat it. Currently, patients with hepatocellular carcinoma only have one treatment option: surgery and a somewhat effective chemotherapy designed for kidney cancer. But progress is being made in this field. Researchers have discovered a new molecule that shows promise for additional chemotherapy treatments.
The research uses oncogene addiction, a technique in which the disruption of one cellular protein leads to the death of the cancer cell. In this case, that protein is LSF. LSF is found in all human cells and organs, but is more abundant in tumor cells. The high levels of LSF in liver cancer cells lead to the growth of the cancerous tumors. Scientists used to think it was impossible to create a drug targeting LSF, however, this compound changed their minds.
Factor quinolinone inhibitor 1 (FQI1) is a compound made from lead that has been shown to target the protein LSF in mice, and human patient tissue samples. By inhibiting the protein, it was able to kill liver cancer cells and prevent tumor growth. Many chemotherapy drugs are able to kill cancer cells, but the problem is they also kill healthy cells. What makes this finding so important is that it killed only the cancer cells, leaving the surrounding non-cancerous cells untouched.
This finding has set the groundwork for a chemotherapy option specific to hepatocellular carcinoma that only kills cancerous cells. This drug has the potential to save many lives and increase the survival rate of a devastating disease affecting people across the globe.
Grant, T.J., Bishop, J.A., Christadore, L.M., Barot, G., Chin, H.G., Woodson, S., Kavouris, J., Siddiq, A., Gredler, R., Shen, X., Sherman, J., Meehan, T., Fitzgerald, K., Pradhan, S., Briggs, L.A., Andrews, W.H., Sarkar, D., Schaus, S.E., and Hansen, U. (2012). Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma. PNAS, 109 (11), 1-6. Doi:10.1073/pnas.1121601109