According to estimates in US approximately 6 – 14% of newly diagnosed patients will develop brain metastases. Almost 45% of patients with lung cancer will develop brain metastases, based on statistical data. Unfortunately there is a poor prognosis for patients with brain metastases. Often by the time they are identified they are no operable and the treatment options are quite limited.
What are the challenges in research?
- Brain metastases are usually secondary tumour site and so far the research is focused on preventing and treating primary tumours.
- The unique nature of the brain and its interactions with cancer cells make it difficult to study with in vitro models. The in vivo models also have their limitations – high mortality rates of lab test mice.
- Mouse models may not be adequate to reflect human brain metastases.
Why the brain is different?
Brain has highly specialized cells, neurons, which allow signals to be transmitted and received throughout the whole body. One of the specific features of the brain is blood-brain barrier (BBB), which controls the flow to the brain and vice versa. Not surprisingly then the first thing the cancer cells have to do when they reach the brain is to pass through the blood-brain barrier. When cancer cells arrive at blood-brain barrier they have to arrest the blood vessels first, which is quite complex process. So far it is observed that cancer cells managed to penetrate blood-brain barrier by passing between the cells, but they can also kill the endothelial cells of the BBB. Once they penetrate BBB cancer cells use different mechanisms to spread. Current data shows that the mechanism that they will use depend on the primary tumour (breast, lung, etc.). Brain cells, known as astrocytes, are the first one to attack cancer cells and try to neutralise them, however cancer cells block astrocytes. High jacking astrocytes also allow cancer cells to develop chemotherapy resistance. Brain is also protected by immune system, cells known as microglia. Microglia originates from bone marrow and can produce macrophages which can eliminate cancer cells. How cancer cells overcome microglia is still unknown due to difficulties to design such experiments.
There are still many unknown in brain metastases mechanism and real challenges in studying these mechanisms.