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Our body does nothing but trip us up in attempts to fight cancer

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Millions of years of evolution have created a tremendously effective immune system when it comes to keeping us safe from 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 counterpart: the barriers that protect our brain also protect cancers that appear in it.

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 tissue that act as a filter or barrier, the blood-brain barrier. This filter allows the passage of water, oxygen and other substances while keeping others out of our brain.

Oncologists have to face a problem derived from overzealousness of this barrier: some treatments are not able to cross this barrier. Thus, perfectly useful treatments for fighting cancer in the rest of the Body are totally ineffective against tumors in our brain.

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Overcoming the difficulties.
Finding ways to circumvent this barrier is among the priorities of many oncologists, including a team from the Vall d’Hebron Institute of Oncology (VHIO). In a paper recently published in the journal CancerResearcha group of researchers led by VHIO scientists has found a way to overcome this barrier.

It is a compound called C1a, an inhibitor of the BRAF gene. BRAF (B-Raf proto-oncogene) is a gene related 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 melanoma cases.

BRAF inhibitors play a key role in the treatment of this type of cancer along 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, since this type of therapy generates some resistance after prolonged use.

Fight the resistance.
That is why part of the team’s work has been to better study the mechanisms of this resistance to delay it as long as possible through 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.

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Fight against melanoma.
Melanoma is the deadliest of skin cancers in number of fatal cases, 57,000 in 2020, and its incidence is on the rise. In Spain alone, melanoma affects 9.7 out of every 100,000 people, 4,000 cases a year.

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

More barriers.
Cancers rarely begin in the brain, but many tumors develop in the brain after metastasis. In any of the cases, the different barriers that oncologists must cross to eradicate this disease are numerous.

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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 brains, complicating any surgical options, including the ability to sample the tumor.

The brain also presents a barrier, this one more metaphorical, when it comes to intervening in cancer, and that is that its characteristically tangled shape seems to mark the direction of tumors, which do not grow in this organ in the same way as in the rest.

The way to go.
For now, the treatment is in its early stages of 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 studying whether it is safe and effective and how it compares to other treatments (including placebo).

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