EGFR, also called HER-1/ErbB1, is a receptor tyrosine kinase (TK) of the ErbB gene family, which contains four closely related proteins, i.e., www.selleckchem.com/products/DAPT-GSI-IX.html HER-1/ErbB1, HER-2/neu/ErbB2,

HER-3/ErbB3, and HER-4/ErbB4. The EGFR gene is located at chromosome 7p12 and encodes a 170 kDa membrane glycoprotein. Upon binding of specific ligands, such as epidermal PRIMA-1MET solubility dmso growth factor and transforming growth factor-α, the receptor forms homodimers, leading to receptor autophosphorylation and activation of the signal cascade. This results in changes in expression of different genes that are crucial to tumor progression, including tumor growth, resistance to apoptosis, invasion, and angiogenesis [8]. TK activity of EGFR is frequently observed in NSCLC, which maybe dysregulated by several oncogenic mechanisms, including EGFR gene mutation, increased gene copy number, and EGFR protein overexpression [9], as in HER-2, although to a significantly lesser extent [10]. Therefore, targeting of EGFR has achieved significant effects in the clinic; however, elevated EGFR activity is more frequent in never-smokers buy EX 527 than smokers, so is less effective in smoking-related lung cancers [11]. In addition, the side effects associated with EGFR

targeting necessitate continued research for more specific molecular targets. KRAS, also known as GTPase KRAS, belongs to the RAS gene family which encodes for a small protein with a molecular weight of 21 kDa with guanosine triphosphatase (GTPase) activity.

KRAS acts as a molecular on/off switch. Once it is turned on it recruits and activates proteins necessary for the propagation of growth factors and other receptors’ signals, such as c-Raf and PI 3-kinase, involved in many signal transduction pathways [12, 13]. The protein product of the normal KRAS out gene performs an essential function in normal tissue signaling, and the mutation of a KRAS gene is an essential step in the development of many cancers. Other members of the RAS family include HRAS and NRAS. These proteins all are regulated in the same manner and appear to differ largely by their sites of action within the cell. Previous studies have demonstrated that expression of KRAS was increased in NSCLC, mutations of which were tobacco smoke-related [14]. Although some studies showed that KRAS and EGFR mutations are mutually exclusive and exhibit contrasting characteristics such as clinical background, pathological features of patients, etc., the actual correlation between these two genes and the effective therapeutics for KRAS mutation in NSCLC are still unclear. RBM5 is one of the approximately 35 genes located in the 370-kilobase tumor suppressor locus on chromosome 3p21.3, loss of which is the most frequent and earliest event in NSCLC [15].