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Targeting the multifaceted BRAF in cancer: New directions
Activating mutations in the mitogen-activated protein kinase (MAPK) pathway represent driver alterations governing tumorigenesis, metastasis, and therapy resistance. MAPK activation predominantly occurs through genomic alterations in and . BRAF is an effector kinase that functions downstream of and...
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| Published in: | Oncotarget 2024-07, Vol.15 (1), p.486-492 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 492 |
| container_issue | 1 |
| container_start_page | 486 |
| container_title | Oncotarget |
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| creator | Toye, Eamon Chehrazi-Raffle, Alexander Hwang, Justin Antonarakis, Emmanuel S |
| description | Activating mutations in the mitogen-activated protein kinase (MAPK) pathway represent driver alterations governing tumorigenesis, metastasis, and therapy resistance. MAPK activation predominantly occurs through genomic alterations in
and
. BRAF is an effector kinase that functions downstream of
and propagates this oncogenic activity through MEK and ERK. Across cancers,
alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I
alterations (p.V600 hotspot mutations) in tumors such as melanomas, thyroid cancers, and colorectal cancers. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in some cancers. Here we discuss the diverse forms of
alterations found in human cancers and the strategies to inhibit them in patients harboring cancers of distinct origins. |
| doi_str_mv | 10.18632/oncotarget.28612 |
| format | article |
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and
. BRAF is an effector kinase that functions downstream of
and propagates this oncogenic activity through MEK and ERK. Across cancers,
alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I
alterations (p.V600 hotspot mutations) in tumors such as melanomas, thyroid cancers, and colorectal cancers. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in some cancers. Here we discuss the diverse forms of
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and
. BRAF is an effector kinase that functions downstream of
and propagates this oncogenic activity through MEK and ERK. Across cancers,
alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I
alterations (p.V600 hotspot mutations) in tumors such as melanomas, thyroid cancers, and colorectal cancers. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in some cancers. Here we discuss the diverse forms of
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and
. BRAF is an effector kinase that functions downstream of
and propagates this oncogenic activity through MEK and ERK. Across cancers,
alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I
alterations (p.V600 hotspot mutations) in tumors such as melanomas, thyroid cancers, and colorectal cancers. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in some cancers. Here we discuss the diverse forms of
alterations found in human cancers and the strategies to inhibit them in patients harboring cancers of distinct origins.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>39018217</pmid><doi>10.18632/oncotarget.28612</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncotarget, 2024-07, Vol.15 (1), p.486-492 |
| issn | 1949-2553 1949-2553 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11254297 |
| source | PubMed Central |
| subjects | Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Humans MAP Kinase Signaling System - genetics Molecular Targeted Therapy Mutation Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism |
| title | Targeting the multifaceted BRAF in cancer: New directions |
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