[The Lancet] Breakthrough!

This article is original by Translational Medicine.
Please indicate the source for reprinting.
Author: Daisy Guide: Recently, a study published on "The Lancet Oncology" showed that for the first time in a clinical trial, researchers have proved that two targeted drugs are effective for patients.
Tumors that carry a mutation in the BRAF gene called V600E are effective for gliomas, showing unprecedented activity, including glioblastomas that are resistant to treatment
.

The BRAF V600E mutation drives cancer by activating the MAPK pathway composed of many proteins, leading to uncontrolled cell growth and tumor development
.

The two drugs are dabrafenib and trametinib, which can block some of the overactive MAPK signaling pathways
.

These patients have not been cured, but patients who responded to the medications received significant and lasting benefits
.

This research breaks the view that people have always believed that "there will never be any targeted therapy for glioblastoma
.
"
According to a clinical trial report by researchers from the Dana Farber Cancer Institute, the combination therapy of two targeted anti-cancer drugs showed unprecedented "clinical significance" activity in patients with highly malignant brain tumors carrying rare gene mutations
.

Recently, researchers published the results of this new study in "The Lancet Oncology" and published an article entitled "Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre , open-label, single-arm, phase 2, basket trial" article: This combination of drugs blocks overactive cell growth signaling pathways.
Among 45 patients with difficult-to-treat high-grade glioma, one-third One patient's tumor shrank by 50% or more, including the most aggressive brain tumor-glioblastoma
.

These patients were selected for the trial because their tumors carry a mutation in the BRAF gene called V600E
.

This mutation is only found in 2-3% of patients with high-grade gliomas, but it is found in up to 60% of low-grade gliomas
.

The study included 13 patients with low-grade glioma
.

Among these patients, 9 had an objective response to the combination therapy, and the effective rate was 69%
.

Patrick Wen, MD, the first author of the "The Lancet Oncology" report, from Harvard Medical School and director of the Dana Farber Neuro-Oncology Center, said: "This is the first clinical trial to prove that any targeted drug is effective against glioblastoma.

.

All current chemotherapy treatment for glioblastoma, the efficiency of not more than 5%, while the effective rate of 33% combined with chemotherapy
.

40 patients under the age of efficiency even higher, about 40%
.

"The two drugs paired in the study are dabrafenib and trametinib
.

Both drugs target proteins in the MAPK pathway.
The MAPK pathway is a protein signal chain.
With the function of the cell growth switch, it can be stuck in the "on" position, causing uncontrolled growth and causing tumors
.

Three patients had complete remission, and their tumors were no longer visible on imaging scans, and 12 patients Some of the tumors have shrunk
.

These patients were not cured, but an evaluation showed that those who responded to the drug received significant lasting benefits, with a median duration of response of 13.
6 months, while another evaluation showed a response duration of 36.
9 months
.

a study called ROAR (Rare Oncology Agnostic Research) phase II study results from the study since 2014 has been enrolling patients in 27 academic and community cancer centers in 13 countries
.

this The study is a so-called "basket" trial that aims to recruit patients with common tumor characteristics (BRAF V600E mutation in this case), although they may have a range of different cancers
.
The
ROAR study includes thyroid cancer and biliary cancer, and gastrointestinal cancer.
Road between patients stromal tumors, hairy cell leukemia, multiple myeloma, low grade and high grade glioma brain tumors
.

this study aimed to determine tadalafil Nepalese joint Qumei imatinib therapy in patients with BRAF V600E mutation of the total cancer Efficiency
.

BRAF protein is a growth signal protein kinase that plays a role in regulating the MAPK signaling pathway
.
The
BRAF V600E mutation drives cancer by activating the MAPK pathway composed of many proteins, leading to uncontrolled cell growth and tumor development
.

The drugs dabrafenib and trametinib used in this study are oral drugs that can block part of the overactive MAPK signaling pathway
.

Dabrafenib inhibits an enzyme, B-Raf, and trametinib inhibits molecules called MEK1 and MEK2, which are part of the MAPK pathway
.

They are used in combination to treat melanoma, non-small cell lung cancer and thyroid cancer
.

Gliomas are cancers that originate in the glial-the supporting cells of the brain-rather than the brain neurons themselves
.

Glioma accounts for about 80% of all malignant brain tumors
.

Some are slow-growing low-grade gliomas, while others are aggressive high-grade gliomas, including glioblastomas that are difficult to remove and almost always recur
.

The author of the report said that in recent years there has been no major progress in the treatment of gliomas, but there are individual reports showing that the combination of dabrafenib and trametinib has shown activity in the treatment of gliomas
.

Their report in the ROAR study stated that “it is the first time that the combination of BRAF inhibitor (dalafenib) and MEK inhibitor (trametinib) has shown activity in these difficult-to-treat gliomas, including historical treatment Glioblastoma that exhibits drug resistance
.

"Although these drugs are only helpful for patients with tumors with rare V600E mutations, Wen said the results are encouraging, "because people are beginning to think that there will never be any targeted glue.
Targeted therapy for plasmoblastoma
.

" He added that emerging evidence suggests that there may be other targets in glioma that can be blocked by designed drugs
.

Reference materials: https://medicalxpress.
com/news/2021-11-drug-combination-unprecedented-highly-aggressive.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.

If you need health guidance, please go to a regular hospital
.

Recommendation·Activity [Live] Clinical Application and Progress of Whole Exome Sequencing (WES) in Genetic Diseases Practitioners-Single Cell Research Creation Camp (Guangzhou Station) Popular·Articles Tumor Research [eLife] Benign Mole Degeneration For malignant melanoma, what happened in the middle? Gut Microorganisms [BMJ Sub-Journal] Why do good foods suddenly become intolerant? New research has identified a unique profile of gut bacteria that is highly sensitive to dietary therapy for irritable bowel syndrome, the new coronavirus [Nature sub-Journal] Human genetics perspective-how genetic mutations affect our immune cells, resulting in different severity of COVID-19 Virus [Nature Sub-Journal] Appropriate vitamin D supplementation can fight inflammation, including new coronary pneumonia! Cancer Research [Cell Sub-Journal] MIT researchers have discovered a secret way to fight tumors-wear tumor cell vests and kill tumor cells! Basic research [Nature Sub-Journal] is amazing! 3D images of mouse skulls help scientists create new bones! Basic research [ATS Sub-Journal] Breakthrough! To map the most comprehensive molecular roadmap of human lung proteins, scientists identified and measured 8,938 proteins!