The mechanism and consequences of BRAF inhibitor resistance in melanoma

Golub, Ksenia; Bai, Weiyu; Zhang, Zhimeng; Xiao, Huilin; Sun, Rongyuan; Shen, Junling; Sun, Jianwei

doi:10.1007/s42764-023-00105-5

Cited by 6 publications

(5 citation statements)

References 64 publications

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“…The discovery of mutant specific BRAF inhibitors, such as vemurafenib, has remarkably improved the survival of melanoma patients with oncogenic BRAF mutations[24]. However, vemurafenib resistance is still the main obstacles for the treatment of melanoma, and the mechanism of vemurafenib resistance induced melanoma invasion and metastasis is still not completely understood[25].…”

Section: Discussionmentioning

confidence: 99%

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The EGF/EGFR-YAP1/TEAD2 axis-mediated BRAF inhibitor vemurafenib resistance upregulates STIM1 in melanoma

Bai,

Yan,

Yang

et al. 2024

Preprint

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STIM1 is the endoplasmic reticulum (ER) Ca2+ sensor for store-operated entry (SOCE) and closely correlated to carcinogenesis and tumor progression. Previously we found that STIM1 is upregulated in melanoma cells resistant to the BRAF inhibitor vemurafenib, but the regulation mechanism is unknown. Here, we show that vemurafenib resistance upregulates STIM1 through an EGF/EGFR-YAP1/TEAD2 axis. Vemurafenib resistance can lead to the increase of EGF and EGFR levels to activate the EGFR signaling pathway. Reactivated EGFR signal promotes YAP1 nuclear localization to increase the expression of STIM1. Our finding not only demonstrates the mechanism by which vemurafenib resistance promotes STIM1 expression, but also provides combined targeting EGF/EGFR-YAP1/TEAD2-STIM1 to improve the therapeutic efficiency of BRAF inhibitor in melanoma patients.

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Section: Discussionmentioning

confidence: 99%

“…However, vemurafenib resistance is still the main obstacles for the treatment of melanoma, and the mechanism of vemurafenib resistance induced melanoma invasion and metastasis is still not completely understood [25].…”

Section: Discussionmentioning

confidence: 99%

The EGF/EGFR-YAP1/TEAD2 axis-mediated BRAF inhibitor vemurafenib resistance upregulates STIM1 in melanoma

Bai,

Yan,

Yang

et al. 2024

Preprint

Self Cite

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“…There are phenotypes associated with both high and low expression of MITF that lead to resistant states, act as a switch between invasive and proliferative stages, and offer an example of tumor plasticity [ 105 , 106 ]. STAT3 (signal transducer and activator of transcription 3) is another important driver for oncogenic stimulation via upregulation of the Mcl-1 (induced myeloid leukemia cell differentiation protein) gene, and its suppression has been shown to be effective in vemurafenib-resistant and -sensitive cells [ 107 ].…”

Section: Mechanism Of Resistance To Braf/mek Inhibitorsmentioning

confidence: 99%

Molecular Targeting of the BRAF Proto-Oncogene/Mitogen-Activated Protein Kinase (MAPK) Pathway across Cancers

Shan,

Rehman,

Ivanov

et al. 2024

IJMS

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The mitogen-activated protein kinase (MAPK) pathway is essential for cellular proliferation, growth, and survival. Constitutive activation of this pathway by BRAF mutations can cause downstream activation of kinases, leading to uncontrolled cellular growth and carcinogenesis. Therefore, inhibition of BRAF and the downstream substrate MEK has been shown to be effective in controlling tumor growth and proliferation. Over the last decade, several BRAF and MEK inhibitors have been investigated, ranging from primarily melanoma to various cancer types with BRAF alterations. This subsequently led to several Food and Drug Administration (FDA) approvals for BRAF/MEK inhibitors for melanoma, non-small cell lung cancer, anaplastic thyroid cancer, colorectal cancer, histiocytosis neoplasms, and finally, tumor-agnostic indications. Here, this comprehensive review will cover the developments of BRAF and MEK inhibitors from melanomas to tumor-agnostic indications, novel drugs, challenges, future directions, and the importance of those drugs in personalized medicine.

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“…Such as, in melanoma, mitochondrial dysfunction contributes to resistance against BRAF inhibitors. 185 These inhibitors target the MAPK pathway, but dysfunctional mitochondria reduce drug effectiveness. 185 …”

Section: Metabolic Reprogrammingmentioning

confidence: 99%

“… 185 These inhibitors target the MAPK pathway, but dysfunctional mitochondria reduce drug effectiveness. 185 …”

Section: Metabolic Reprogrammingmentioning

confidence: 99%

Hallmarks of cancer resistance

Tufail,

Hu,

Liang

et al. 2024

iScience

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The mechanism and consequences of BRAF inhibitor resistance in melanoma

Cited by 6 publications

References 64 publications

The EGF/EGFR-YAP1/TEAD2 axis-mediated BRAF inhibitor vemurafenib resistance upregulates STIM1 in melanoma

The EGF/EGFR-YAP1/TEAD2 axis-mediated BRAF inhibitor vemurafenib resistance upregulates STIM1 in melanoma

Molecular Targeting of the BRAF Proto-Oncogene/Mitogen-Activated Protein Kinase (MAPK) Pathway across Cancers

Hallmarks of cancer resistance

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