MEK Inhibitor FCN-159 To Treat Advanced Melanoma With NRAS-aberrant (Ia) and NRAS-mutant (Ib)

MEK Inhibitor FCN-159 To Treat Advanced Melanoma With NRAS-aberrant (Ia) and NRAS-mutant (Ib)

Publication date: Apr 30, 2019

Melanoma is one of the most common cutaneous cancers worldwide. Activating mutations in RAS oncogenes are found in a third of all human cancers and NRAS mutations are found in 15%-20% of melanomas. Acquisition of a functional mutation in NRAS results in activation of the Ras / Raf / MEK / ERK signaling pathway leading to unconstrained cell growth and cell transformation. NRAS mutation status was identified as an independent poor prognostic factor in stage IV melanoma. No drug was approved to treat melanoma patients with NRAS mutation or amplification until now. FCN-159, an oral and potent MEK1/2 inhibitor, has more than 10 folds higher selectivity against activated MEK1 and MEK2 compared with trametinib, and has demonstrated significant antitumor growth inhibition in two patient-derived xenograft (PDX) models with NRAS mutation.This is the first in human study to evaluate the safety and anti-tumor activity in patients.

Concepts Keywords
Abstinence Tumors
AJCC HIV
Alanine Aminotransferase Diseases
Albumin Congestive heart failure
Allergic Melanoma
Alopecia Common cutaneous cancers
ALT QTc interval Dysphagia
ANC Cancers
Antigen Hepatitis hepatitis
Arrhythmias Safety anti tumor
Aspartate Aminotransferase Alopecia
AST Chemotherapy
Atrioventricular Block Radiation
Bilirubin Melanoma
Bleeding Branches of biology
Chemotherapy Cancer
Cohort RTT
Common Ras subfamily
Congenital MEK inhibitor
Congestive Heart Failure Neoplasms
Contraceptive Health
Cooperative Group Vemurafenib
Creatinine Pharmacokinetics
Cytochrome Radiation
Cytologically 3g
Digestive System Chemotherapy
Dysphagia
ECG
Electrocardiogram
ERK
Excipients
Failure Rate
Fertility
Formula
Fungal
Glaucoma
Hemoglobin
Hemolysis
Hemolytic
Hepatitis
Heterosexual
Histologically
HIV Positive
Immunodeficiency
Infection
Inhibitor
IU
Lactating
Lesion
Liver
Malabsorption Syndrome
MEK
Melanoma
Melanomas
Metastases
Mutant
Mutation
NCI
Neurotoxicity
Oncogenes
Organ
Paraffin
Pharmacokinetics
Platelets
Pneumonia
QTc Interval
RAS
Ras
Retinal Detachment
Shanghai
Stenosis
Titration
Transfusion
Tumor
Viral
Virus
Xenograft

Semantics

Type Source Name
drug DRUGBANK Pralatrexate
disease MESH growth
drug DRUGBANK Trametinib
gene UNIPROT MAP2K2
gene UNIPROT MAP2K1
gene UNIPROT EPHB2
gene UNIPROT MAPK1
gene UNIPROT ZHX2
drug DRUGBANK Rasagiline
disease MESH cancers
gene UNIPROT NRAS
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma
gene UNIPROT MAP2K7
disease DOID Cancer
disease MESH hemolysis
disease MESH congenital
gene UNIPROT SLC17A5
drug DRUGBANK L-Alanine
disease MESH metastases
drug DRUGBANK Creatinine
drug DRUGBANK Methionine
gene UNIPROT SLTM
gene UNIPROT MET
gene UNIPROT RNMT
disease MESH alopecia
disease DOID alopecia
disease DOID neurotoxicity
disease MESH bleeding
gene UNIPROT CYP3A4
disease MESH Dysphagia
disease MESH digestive system disease
disease MESH malabsorption syndrome
disease MESH stenosis
disease MESH retinal detachment
disease DOID retinal detachment
disease DOID central retinal vein occlusion
disease MESH glaucoma
disease DOID glaucoma
disease MESH Interstitial pneumonia
disease MESH pneumonitis
disease MESH electrocardiogram
disease MESH congestive heart failure
disease DOID congestive heart failure
disease MESH abnormalities
disease MESH atrioventricular block
disease DOID atrioventricular block
disease MESH viral infections
disease MESH hepatitis B
disease DOID hepatitis B
pathway BSID Hepatitis B
disease MESH hepatitis C
disease DOID hepatitis C
pathway BSID Hepatitis C
disease DOID virus infection
gene UNIPROT IMPACT

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