RAS-RAF-MEK-ERK PATHWAY

MAPK/ERK pathway

EGF -> EGFR -> GRB-2 -> SOS -> RAS -> RAF -> MEK -> ERK -> Transcription Factors -> Cell Proliferation, Survival, Metastasis

ERK

Extracellular Regulated Kinase; activates latent transcription factors like MAPK, c-myc, c-jun, c-fos, ets.

EGF

epidermal growth factor

N-ras

melanomas, hematologic malignancies

B-Raf

serine/threonine kinase over expressed in MELANOMA, Non Hodgkin's lymphoma, colorectal cancer, papillary carcinoma of the thyroid; Point Mutation

RAF

1. 3 variants RAF-A, RAF-B, RAF-C; 2. Regulated by PFK, SRC, HSP90, 14-3-3 3. Phosphorylates MEK1/2 4. Melanoma, Thyroid, Colon Cancer

RAS

1. Has 3 variants H-RAS, K-RAS, & N-RAS; 2.Phosphorylates RAF 3. Thyroid, Colon, Endometrial, Lung Adenocarcinomas, Myeloid Leukemias Cancer.

EGFR

1. epidermal growth factor receptor; 2. Phosphorylates GRB2; 3. Activated by TGFa, EGF, Betacelluim, & Epiregulin. 4. Over-expression = Increased MAPK/ERK pathway 5. Lung, Colorectal, Pancreatic Cancer

RAS drugs

Binimetinib: Inhibits MEK1/2

SOS

Gaunine Nucleotide exchange factor; Phosphorylates RAS

Grb2

Growth factor receptor bound protein 2; binds SOS

K-ras

Lung ca, colon ca, & Pancrease ca

MEK1/2

MItogen Activated Protein Kinase; Phosphorylates ERK

EGFR drugs

Mab: Cetuximab Tinib: Erlotinib, Afatinib

MAPK/ERK pathway

RAS-RAF-MEK-ERK; Goal Cell Proliferation, Survival, Metastasis.

H-RAS

bladder and kidney tumors