melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Specific mutations of RAF kinases, such as the prevalent BRAF(V600E) mutation in melanoma, or defects in upstream signaling or feedback loops cause decoupled kinase activities which lead to tumorigenesis.
|
28466200 |
2019 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Recent clinical and therapeutic success with RAF and MEK1/2 inhibitors has revolutionized the existing treatment schemes for previously incurable cancers like melanomas.
|
31662208 |
2019 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Malignant melanoma with areas of rhabdomyosarcomatous differentiation arising in a giant congenital nevus with RAF1 gene fusion.
|
30945443 |
2019 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Hyperactivation of MAPK Signaling Is Deleterious to RAS/RAF-mutant Melanoma.
|
30201825 |
2019 |
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Targeted inhibition of RAF and MEK by molecularly targeted agents has been employed as a strategy to block aberrant mitogen-activated protein kinase (MAPK) signaling in melanoma.
|
30622172 |
2019 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven by the activated BRAF oncogene.
|
29343524 |
2018 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Reduced RB abundance, in turn, impairs E2F1 transcriptional inhibition, leading to increased peptidyl-prolyl cis-trans isomerase never-in-mitosis A (NIMA)-interacting 1 (PIN1) levels, human keratinocyte neoplastic cell transformation, and melanoma tumorigenesis via enhanced rapidly accelerated fibrosarcoma 1(RAF1)-MEK-ERK signaling pathway activation.
|
29750576 |
2018 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer.
|
28082416 |
2017 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance.
|
28984291 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Despite low activity at tolerable doses, this study provides a framework for the development of pan-RAF inhibitors and modulators of angiogenesis for the treatment of melanoma.
|
28719152 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Kinase inhibitors targeting RAF or MEK are already used for the treatment of certain cancers, such as melanoma.
|
28740606 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM.
|
27786364 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
MAPK and Hippo signaling pathways crosstalk via the RAF-1/MST-2 interaction in malignant melanoma.
|
28677804 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven melanoma.
|
28497782 |
2017 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Protein Kinase CK2α Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2α Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma.
|
27226552 |
2016 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
RAF inhibitors represent the emerging standard of care for metastatic BRAF mutated melanomas.
|
25296968 |
2016 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Ongoing studies include combinations of CDK4/6 inhibitors with endocrine therapy and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors for hormone receptor-positive (HR+) breast cancers, and with selective RAF and MEK inhibitors for tumors with alterations in the mitogen activated protein kinase (MAPK) pathway such as melanoma.
|
27017286 |
2016 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas.
|
27273450 |
2016 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V) (600E) melanoma.
|
25814555 |
2015 |
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma.
|
25645078 |
2015 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
RAF inhibitors are an effective therapy for patients with BRAF-mutant melanoma and brain metastasis.
|
25956405 |
2015 |
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Although RAF inhibitor monotherapy is highly effective in BRAF-mutant melanoma, response rates in BRAF-mutant colorectal cancer are poor.
|
25673644 |
2015 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Here, we summarize and evaluate the human relevance of various RAF and RAS mouse melanoma models and their contribution to our understanding of melanoma.
|
24342721 |
2015 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations.
|
26351322 |
2015 |
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC).
|
25801412 |
2015 |