Colon cancer. Metastases to brain. New treatment and prevention. 4

Metastatic spread of tumor requires cancer cells to travel to hostile “foreign” organs and tissues. Thus tumor cells acquire new mutations. Leading oncologist and precision medicine expert explains new research. How to predict and prevent metastatic spread of cancer. Especially spread of colorectal cancer to the brain.

Dr. Anton Titov, MD. You are studying metastasis, or spread, of cancer cells into other organs. Metastases spread to lungs, liver, but especially to the brain. Dr. Anton Titov, MD. You identified particular mechanisms how colorectal cancer cells can spread to the brain. What causes spread of cancer cells to the brain? Dr. Anton Titov, MD. what can prevent the metastatic process into the brain from, for example, colorectal cancer? Dr. Anton Titov, MD. Dr. Ido Wolf, MD. This is a project that we just recently started. So it is a brand new research in our lab and what we do. We take various tumors. We study colon cancer, pancreatic cancer, breast cancer. We see what affects the spread of metastasis. This is an important question. Because many of the studies that were done today, including genomic studies or RNA sequencing focused mostly on the primary tumor. Because this is the tumor tissue that usually cancer researchers have from a surgeon or pathologist. What we are now discovering is this. Most of these cancer discoveries are brand new, they are not even published yet. What we do see is this. Specific metastasis in specific organs have specific mutation pattern. Why is that important? Dr. Anton Titov, MD. Because we know that the environment in the brain or in the liver is completely different from the environment in the primary tumor. For example, let’t talk about breast cancer. The breast tissue is completely different from the liver tissue. Let’s talk about colon cancer. The colon itself is completely different from the brain. Dr. Ido Wolf, MD. That means that the cancer cells need to adapt to a whole new environment. The adaptation requires adapting to lower oxygen levels. It requires adaptation to low glucose levels. Dr. Ido Wolf, MD. That adaptation requires a whole network of metabolic activity that must be switched on. We are now looking at these specific molecular switches. They allow cancer cells to survive and proliferate in a hostile environment. Because for a cancer cell can go from one tissue to another. Environment around metastases may be quite hostile, but cancer cells still manage to do it. We think that at least some of adaptation is done by specific mutations that drive the metastasis. These mutations allow cells to proliferate in these hostile environments. Dr. Ido Wolf, MD. That is very important. Because then you realize that the genetics of the tumor in the primary location can be quite different from metastatic disease. Metastases to the liver and to the brain frequently happen in colorectal cancers. But environment in the liver is very different from the molecular environment in the brain. Different medications could address different targeted mutations. First of all, theoretically, we could know the mutation profiles of the primary tumor. Then we may be able to predict to what other tissue sites cancer will go. We know that a specific tumor mutation pattern may give advantage to go to a specific organ site. Dr. Ido Wolf, MD. One thing is prediction of metastatic cancer location. The other goal is, definitely, treatment of metastatic cancer. We know that you could find specific vulnerabilities of specific metastasis. Then we can target these specific caner vulnerabilities. For example, we could inhibit specific cancer metabolic pathways. Those metabolic pathways are crucial for cancer metastasis. For example, in colorectal cancer, when the cancer metastasized to the brain, that frequently puts patients at the terminal stage of the disease. Dr. Ido Wolf, MD.  Addressing the metastatic lesions in the brain is particularly important! Yes, definitely, and maybe even preventing them. How could you possibly prevent the metastatic spread into the brain? Dr. Anton Titov, MD. For example, by identifying these specific molecular pathways. They exist already in the primary tumor. Then oncologists could try to target them in advance. Dr. Ido Wolf, MD. Prevention is the best treatment, clearly. Yes!