Spring of brain tumor treatment: targeted therapy for the driver gene BRAF has worked!

Glioblastoma is a malignant tumor that occurs in the brain and has been lacking a very effective treatment strategy
.
Although aggressive treatment can be carried out with surgery, radiotherapy, temozolomide, etc.
, these treatment measures have not significantly improved the treatment effect, and the overall survival of patients is limited
.

BRAF gene mutation in glioblastoma

If glioblastoma is to be molecularly tested, it is generally to detect mutations in the IDH gene, methylation of the promoter region of the MGMT gene, and translocation of 1p19q
.
Recently, researchers found a V600E variant
of the BRAF gene in 3% of brain cancer patients.

For the V600E variant of the BRAF gene, in melanoma, lung cancer, and bowel cancer, targeted drug combinations with better efficacy can be used
.
So, will these drugs work in glioblastoma? Let's take a look at the treatment cases
below.

Dabrafenib in combination with trametinib shows therapeutic potential

A 46-year-old woman presents with symptoms of loss of consciousness and epilepsy
in good health without underlying medical conditions.
CT of the head showed a parenchymal hematoma (5.
3 × 4.
1 × 4.
1 cm) of the brain, and the patient underwent emergency surgery and postoperative brain MRI showed a lesion
of 3.
2 × 2.
7 × 3.
8 cm.

The postoperative pathological diagnosis was astrocytic invasive tumor, and molecular testing performed found no mutation in the IDH gene and no methylation
of the MGMT promoter.
Subsequent next-generation gene sequencing revealed V600E mutations in the BRAF gene, TERT and MYC amplification, and loss
of CDKN2A/B genes.

Initially, the patient received chemoradiation and chemotherapy, which was given temozolomide
.
Later, based on the results of molecular tests, the doctor discontinued temozolomide because he considered that the patient was not a potential beneficiary of temozolomide
.
Over the next few months, the patient's brain examination results were stable and motor and cognitive abilities recovered
.

In the 8th month after diagnosis, the patient developed back pain, physiotherapy and conventional symptomatic treatment
.
Two months later, the condition deteriorated further, and MRI of the spine showed diffuse tumor involvement of the vertebrae, accompanied by pathological fractures, epidural extension, and dural sac compression
.
Patients then underwent palliative kyphoplasty, diagnostic biopsy, and microwave ablation
.
The results indicated the presence of a V600E mutation
in the BRAF gene.

Doctors give palliative radiation therapy to the thoracic spine to control pain, but brain and spinal cord imaging shows progression, and PET-CT shows lesions
in the hip and right lung.
Because the patient had a V600E mutation in the BRAF gene, 11 months after initial diagnosis, a combination of BRAF and MEK inhibitors was started with 150 mg of dabrafenib and 2 mg of trametinib
daily.

Fig.
Darafenib in combination with trametinib shown therapeutic potential

As shown in the figure above, the first treatment interval scan showed that the tumor volume of the brain and spine was reduced, and the lesion in the right lung was no
longer there.
The patient tolerated this drug combination and did not experience adverse symptoms
.
After 9 months of overall treatment, the patient's brain lesions remained stable
.
Later, because new metastases could not be effectively controlled, the patient was transferred to hospice care
.

revelation

From the above case, it can be seen that for brain cancer patients with BRAF gene V600E mutations, a combination of dabrafenib, a targeted drug for BRAF gene, and trametinib, a targeted drug for MEK, can achieve a better therapeutic effect
.

For other types of malignant tumors, if a V600E mutation in the BRAF gene is found, you can also refer to the above case
.

It is uncertain whether patients continue to monitor for new resistant lesions during targeted therapy, and whether interspersing temozolomide prolongs the efficacy of targeted drug
combinations.
These measures may help delay the resistance of targeted drugs and benefit patients longer
.

Regarding the treatment combination of targeted drugs, treatment potential, and the analysis and interpretation of genetic testing reports, you are welcome to pay attention to the degree of cancer and consult a cancer medical consultant or similar patients in the community
.

Pay attention to the degree of cancer, take every step of cancer prevention and anti-cancer!

References: Vasu Munjapara, et al.
, BRAF V600E-mutant glioblastoma with extracranial metastases responsive to combined BRAF and MEK targeted inhibition: A Case Report, Case Rep Oncol 2022; 15:909-917;

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