Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.
Mohaddeseh HedayatReza JafariNaime Majidi ZolbaninPublished in: Clinical and experimental medicine (2022)
Cancer incidence is rapidly growing. Solid tumors are responsible for a majority of cancers. Recently, molecular-targeted agents have played a significant role in cancer treatment. Ras-Raf-MEK-ERK signaling pathway, is a substantial element in the survival, propagation, and drug resistance of human cancers. MEK is a specific part of the so-called cascade, and ERK proteins are its sole target. Furthermore, their downstream position in the Ras-ERK cascade, is noteworthy to direct their function in patients with upstream mutated genes. MEK1 mutations are responsible for initiating several solid tumors. Selumetinib (AZD6244) is a second-generation, selective, potent, and non-ATP competitive allosteric MEK1 inhibitor. The efficacy of selumetinib in various solid tumors such as colorectal cancer, lung cancer, neurofibroma, and melanoma is investigated. The present paper provides an overview of the MAPK cascade, the role of selumetinib as a MEK1/2 inhibitor, and the related findings of clinical trials for solid tumor treatment.
Keyphrases
- pi k akt
- signaling pathway
- cell proliferation
- clinical trial
- induced apoptosis
- epithelial mesenchymal transition
- endothelial cells
- risk factors
- papillary thyroid
- wild type
- squamous cell carcinoma
- young adults
- small molecule
- genome wide
- gene expression
- single molecule
- oxidative stress
- combination therapy
- dna methylation
- induced pluripotent stem cells
- replacement therapy
- open label
- genome wide identification
- phase ii
- high speed