Metastases are the major cause of death from cancer. Liver is one of the top three organs (next to bone and lung) to be colonised by metastazing tumors. Studying hepatic metastases is thus an important component of developing new targeted therapies. Unfortunately, tumors harbour a heterogenous cell population, some of which are able to survive treatment. Based on available genetic data, the extent of tumor heterogeneity appears vast and unpredictable. But researchers from the University of Liège recently showed that cancer cells are not necessarily so heterogeneous at the protein level. They were also able to identify two potential targets for colorectal carcinoma (CRC) liver metastases.

Colon cancer or colorectal cancer is one of the most common cancers, afflicting both men and women. According to the World Health Organisation (WHO), more than 600,000 of the 7.6 million worldwide cancer deaths in 2008 were from colon cancer. One of the characteristics of cancer is the abnormally rapid and uncontrolled proliferation of cells that can spread to other bodily organs. Theses metastases are the main cause of cancer deaths. 

At the time of diagnosis, people with colon cancer have metastases in 20-30% of cases. "When the tumour cells invade through the colon walls, the liver is often the first organ to develop metastases. Liver metastasis are also frequent in breast cancer, lung cancer, pancreas cancer and many others" explains Andrei Turtoi, FRS-FNRS Research Fellow with the GIGA-Cancer Metastasis Research Laboratory at ULg. The liver is thus a key element in the study of metastases.

When surgery is not enough

As long as no metastases develop, colon cancer can be cured. But when metastases reach the liver, only 30% of patients are operable. While this minority performs better (25% survive 5 years), 95% of non-operable patients die within next 5 years. "For 70% of patients with liver metastases, surgery isn't an option," emphasises Andrei Turtoi. "This is why scientists are trying to find other kinds of treatment for metastases and particularly those in the liver." Today there are high hopes for targeted therapy. This term refers to medication that acts on a particular protein or a mechanism involved in tumour development. Theoretically, these therapies kill cancer cells without damaging healthy tissues. This is in contrast to chemo- or radiotherapy which often cause collateral damage, limiting the possibility to escalate the dose and kill the tumor. "The basic principle of targeted therapy is that it depends on the specific proteins within the tumour. In one kind of targeted therapy, these proteins must be easily accessible so that antibodies or antibody-drug conjugates can reach and bind them," the specialist explains. The chosen protein targets are thus generally proteins that are located on the surface of cancer cells.