Millions of years of evolution have created an immune system that is extremely effective at protecting us against a multitude of threats. But sometimes having such advanced defenses works against us. Allergies are the most obvious example of this, but it may not be the only equivalent: The barriers that protect our brain also protect the cancers that arise in it.

The blood-brain barrier.
We have a network of blood vessels and tissues, a blood-brain barrier that acts as a filter or barrier to protect our most important organ from bacteria and other dangerous agents. This filter allows water, oxygen, and other substances to pass, while keeping others out of our brains.

Oncologists face a problem that arises from the overzealousness of this barrier: some treatments cannot overcome this barrier. Therefore, treatments that are perfectly useful for fighting cancer in the rest of the body are completely ineffective against tumors in our brain.

To overcome difficulties.
Finding ways to overcome this barrier is among the priorities of many oncologists, including a team from the Vall d’Hebron Institute of Oncology (VHIO). In an article recently published in the journal cancer researchA group of researchers led by VHIO scientists has found a way around this hurdle.

It is a compound called C1a, which is an inhibitor of the BRAF gene. BRAF (B-Raf proto-oncogene) is a gene involved in the transfer of information between the outside of the cell and its nucleus, as well as its replication. A mutation of this gene is linked to a significant number of melanoma cases.

BRAF inhibitors, along with MEK inhibitors (another gene also linked to cell growth and division), play an important role in the treatment of this type of cancer. A new treatment based on these inhibitors could also help patients whose cancer has not yet reached the brain, because this type of treatment builds up some resistance after long-term use.

Fight the resistance.
Therefore, part of the team’s work has been to better examine the mechanisms of this resistance to delay it for as long as possible through combined treatments. “This understanding will help identify robust biomarkers of response and ultimately guide patient classification in clinical trials,” said Ester Bonfill-Teixidor, one of the study’s lead authors.

Fight melanoma.
Melanoma is the deadliest skin cancer with 57,000 fatal cases in 2020 and its incidence is increasing. In Spain alone, melanoma affects 9.7 out of every 100,000 people, 4,000 cases per year.

Between 7% and 20% of melanoma cases develop metastases to the brain and can reach 70% in the later stages of the disease.

More obstacles.
Cancers rarely start in the brain, but many tumors develop in the brain after metastasis. In any case, there are many different hurdles that oncologists must overcome to eradicate this disease.

The blood-brain barrier isn’t the only example where our body’s over-zealous effort to protect our brain has caused problems when it comes to cancer treatment. The skull is a new physical barrier. The skull limits access to our brains, complicating any surgical option, including the ability to sample the tumor.

The brain also poses a more figurative barrier when it comes to interfering with cancer, and it’s characteristic that its mixed shape seems to point in the direction of tumors that don’t grow in this organ as well as in this organ. rest.

The way to go.
For now, the treatment is in the early stages of development. For this progress to translate into an approved treatment for fighting cancer, there is still time for testing to be done to ensure its effectiveness and efficacy. Until a treatment is approved, clinical trials involve three clinical trial phases that examine whether it is safe and effective and how it compares to other treatments (including placebo).

Image | Alina Grubnyak