Related Experiment Video
Updated: May 29, 2026
06:44
Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
Published on: March 1, 2024
Role of BRAF in thyroid oncogenesis
Lisa M Caronia1, John E Phay, Manisha H Shah
1Ohio State University College of Medicine, Divisions of Surgical Oncology and Medical Oncology, James Cancer Center & Solove Research Institute, Columbus, OH 43210, USA.
Summary
The BRAF V600E mutation drives thyroid cancers like papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC). Targeting this mutation with inhibitors shows promise for treating these aggressive, iodine-resistant cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- BRAF is a key kinase in the MAPK pathway, crucial for cell signaling.
- The BRAF V600E mutation leads to uncontrolled kinase activity and is prevalent in thyroid cancers.
- This mutation initiates follicular cell transformation in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC).
Purpose of the Study:
- To review the role of BRAF V600E in thyroid cancer development and progression.
- To discuss the diagnostic and prognostic significance of BRAF V600E detection.
- To explore therapeutic strategies targeting BRAF V600E in thyroid cancer.
Main Methods:
- Literature review of studies on BRAF mutations in thyroid cancer.
- Analysis of diagnostic and prognostic data related to BRAF V600E.
- Examination of preclinical and clinical data on BRAF inhibitors and combination therapies.
Main Results:
- BRAF V600E is frequently detected in PTC (44%) and ATC (24%), with high diagnostic accuracy.
- BRAF V600E presence correlates with aggressive, iodine-resistant thyroid cancer phenotypes.
- First-generation BRAF inhibitors like sorafenib show efficacy, but mechanisms are complex; combination therapies show promise.
Conclusions:
- BRAF V600E is a critical driver and therapeutic target in PTC and ATC.
- Accurate detection of BRAF V600E aids diagnosis and prognosis.
- Targeted therapies, including combination treatments, offer potential to alter the clinical course of BRAF V600E-driven thyroid cancers.
Related Concept Videos
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...