Some cancers have a higher risk of spreading to the brain in the form of metastases. Lung cancer, malignant melanoma (skin cancer) and breast cancer, in particular, spread to the brain. So far there have been no really effective treatments for those affected. An important starting point is therefore to inhibit such brain metastases or to prevent them occurring in the first place.
"Research is currently pursuing several approaches to prevention," explains Matthias Preusser, Head of MedUni Vienna's Division of Oncology and member of the joint Comprehensive Cancer Center of MedUni Vienna and AKH Vienna: "Amongst other things, the international research community has discovered that brain metastases need blood vessels in order to grow. There are already clinical studies showing that suppressing angiogenesis (blood vessel formation) successfully inhibits the growth of metastatic tumours."
Another approach is to consider individual risk factors for developing brain metastases. "If we have sufficient understanding of the molecular mechanisms that contribute to brain metastasis, then, in future, we would be able to suppress various activated signalling pathways, to protect the brain against attack by cancer cells," says Preusser, describing this method. Examples are ALK (anaplastic lymphoma kinases) or VEGF (vascular endothelial growth factor) inhibitors that are already used to treat cancer patients. Inhibition of the CDK (cyclin-dependent kinases) signalling pathway might also help to inhibit the formation of brain metastases. Says Preusser: "In a paper in which we participated and which was recently published in Nature Genetics, it was also demonstrated that some cancer cells can settle in the brain early on in the disease so that early targeted treatment could be expedient to prevent seeding of brain metastases."Some chemotherapy drugs are also suitable for preventing or delaying metastasis. For example, it was found in animal models that temozolomide, a chemotherapy drug commonly used against glioblastomas (brain tumours) prevents metastasis, if taken in low doses on a long-term basis.
Recent successes in treatment
"We have high hopes of the advances made in immunotherapy," explains Preusser. Immunotherapy involves activating the patient's own immune system to fight the cancer cells by blockading various signalling pathways on the surface of the cancer cell. The immune system can then recognise them as foreign bodies. Another approach involves targeted therapies that inhibit the specific signalling pathways that are important for the growth and survival of cancer cells. The human brain has its own immune system and is well protected against external influences by the blood-brain barrier. However, it would appear that current cancer drugs nonetheless find their way into the brain, where they are effective against brain metastases in many patients.
Even in radiotherapy it is often more successful not to irradiate the brain as a whole but instead to target the seat of the tumour. This protects the unaffected, healthy areas of the brain.
Research at MedUni Vienna among the global front-runners
With the Comprehensive Cancer Center Vienna jointly established with Vienna General Hospital, MedUni Vienna is among the global front-runners in the field of cancer research. This ensures rapid translation of the latest research findings into clinical practice. "Particularly in the area of brain metastasis, our aim is to prevent it occurring in the first place," explains Preusser, "we want to be able to identify risk groups and provide them with preventive protection against metastasis. As time goes on, we will become increasingly successful at doing this."
Service: Brain Metastasis research symposium
Currently (28/29 June) a high-level specialist symposium is taking place at MedUni Vienna on the subject of research into brain metastasis. The event has been organised by MedUni Vienna's Division of Oncology and the Massachusetts General Hospital Cancer Center.
Quantitative evidence for early metastatic seeding in colorectal cancer.
Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, Suarez CJ, Berghoff AS, Cremolini C, Falcone A, Loupakis F, Birner P, Preusser M, Lenz H, Curtis C.; Nat Genet. 2019 Jun 17. doi: 10.1038/s41588-019-0423-x; www.ncbi.nlm.nih.gov/pubmed/31209394