Colorectal Cancer, Liver Metastasis Focus of ICRF Grant

Dr. Tal Falick Michaeli, an ICRF Postdoctoral Fellowship recipient, talks about the role behavior and environment play in the metastasis of the liver during regeneration, after treatment with resection.

We are particularly interested in your research as it relates to colorectal cancer. Can you describe what you are working on?

Colorectal cancer (CRC) is the third most common cancer in terms of incidence and the fourth in mortality. The liver is the most common site of metastasis in patients with colorectal cancer, with more than 50 percent of patients developing liver metastasis during the first three years following diagnosis. There are several ways to treat liver metastasis; however, the main approach to achieve a cure is by liver resection whenever possible, especially in patients with liver isolated CRC. Although the liver has a remarkable regeneration capacity, after resection, liver metastases recur in about 75 percent of patients. Our research aims to decipher the role of epigenetic (the study of how behaviors and environment can cause changes that affect how genes work) regulation in the regeneration process following hepatic resection in a mouse colorectal liver metastasis model. We are also exploring the altered epigenetic landscape in normal hepatocytes (cells in the liver) adjacent to the transformed cells in a mouse model, as well as in human liver tissues.

What have you accomplished in this area to date, and what do you hope to accomplish in the next year?

Thus far, we have been able to characterize the changes occurring in the hepatocytes in terms of expression and epigenetics when they are exposed to a tumor environment. We have managed to expand our knowledge of the process of liver resection from a detailed molecular developmental perspective. Currently, we are utilizing this data to understand the regeneration process in the metastatic liver.

Our hope for the coming year is that by employing the findings in our mouse model, it will allow us to manipulate the liver regeneration process, and provide a step forward in the future of patient liver resection management.

What, if any, will be the potential impact on patients?

Our experiments will help elucidate the molecular mechanisms that take place in patients following hepatic resection as a result of metastasis formation. These studies should lay the groundwork for understanding how to manage patients approved for hepatic resection prior to, and in the years following surgery.

Any additional comments?

I wish to thank the ICRF for supporting this research as part of its continued participation in the global goal of understanding the mechanisms of cancer in the hope for better treatments and cures. I would particularly like to thank my mentors, Professors Howard Cedar and Yehudit Bergman. I would also like to thank my mentors from the clinic in Hadassah Medical Center, Prof. Aron Popovtzer, Prof. Michal Lotem and Prof. Eli Pikarsky.