Millions of years of evolution have created an extremely effective immune system when it comes to protecting us from a multitude of threats. But sometimes having such advanced defenses works against us. Allergies are the most obvious example, but it is perhaps not the only counterpart: the barriers that protect our brain also protect the cancers that appear there.
The blood-brain barrier.
In order to protect our most important organ from bacteria and other dangerous agents, we have a network of blood vessels and tissues that act as a filter or barrier, the blood-brain barrier. This filter allows the passage of water, oxygen and other substances while keeping the others out of our brain.
Oncologists have to deal with a problem derived from an overzealousness of this barrier: some treatments fail to cross this barrier. Thus, treatments that are perfectly useful for fighting cancer in the rest of the body are completely ineffective against tumors in our brain.
Finding ways to circumvent this obstacle is among the priorities of many oncologists, including a team from the Vall d’Hebron Institute of Oncology (VHIO). In one recently published work in the review Research against cancera group of researchers led by VHIO scientists have found a way to overcome this obstacle.
This is a compound called C1aan inhibitor of gen BRAF. BRAF (B-Raf proto-oncogene) is a gene linked to the transmission of information between the exterior and the nucleus of a cell, but also to its replication. A mutation of this gene is linked to a significant number of cases of melanoma.
The bone BRAF inhibitors they play a key role in the treatment of this type of cancer with MEK inhibitors (another gene also linked to cell growth and division). A new treatment based on these inhibitors could also help patients whose cancer has not yet reached the brain, because this type of therapy generates some resistance after prolonged use.
Fight the resistance.
This is why part of the work of the team consisted in better studying the mechanisms of this resistance in order to delay it as long as possible thanks to combined treatments. “This understanding will help identify robust biomarkers of response and ultimately guide patient stratification in clinical trials,” explained Ester Bonfill-Teixidor, one of the study’s lead authors.
Fight against melanoma.
Melanoma is the deadliest of skin cancer in number of fatal cases, 57,000 in 2020, and its incidence is al raises. Only In Spain melanoma affects 9.7 per 100,000 people4,000 cases per year.
Between 7 and 20% of melanoma cases develop metastases in the brain, and can reach 70% in the advanced stages of the disease.
No more barriers.
Cancers rarely start in the brain, but many tumors develop in the brain after metastasis. In any case, the various barriers that oncologists must overcome to eradicate this disease are numerous.
The blood-brain barrier is not the only example where our body’s overzealousness in protecting our brain leads to problems when it comes to treating cancer. The skull is a new physical barrier. The skull limits access to our brain, complicating all surgical options, including the possibility of taking a sample of the tumor.
The brain also presents a barrier, this one more metaphorically, when it comes to intervening in cancer, and that is that its characteristic tangled shape seems to indicate the direction of the tumorswhich do not grow in this organ in the same way as in the rest.
The way to go.
For the moment the treatment is in early stages of its development. For this advance to translate into an approved treatment for the fight against cancer, there is still time for tests to ensure its effectiveness and efficiency. Clinical trials until a treatment is approved include three phases of clinical trials to find out if it is safe and effective and how it compares to other treatments (including a placebo).
Picture | Alina Grubniak