We conducted global profiling for microRNAs (miRNAs) in a cohort of stage 1 nonsmall cell lung cancers (n = 81) and determined that miR-486 was the most down-regulated miRNA in tumors compared with adjacent uninvolved lung tissues, suggesting that miR-486 loss may be important in lung cancer development. MiR-486 directly targets components of insulin growth factor (IGF) signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer both in vitro and in vivo. Our findings support the role for miR-486 loss in lung cancer and suggest a potential biological link to p53.
“Using a panel of non–small cell lung cancer (NSCLC) lines, we show here that MAP-ERK kinase (MEK) and RAF inhibitors are selectively toxic for the KRAS-mutant genotype, whereas phosphoinositide 3-kinase (PI3K), AKT, and mTOR inhibitors are not. IGF1 receptor (IGF1R) tyrosine kinase inhibitors also show selectivity for KRAS-mutant lung cancer lines.”
Preliminary results from an ongoing phase II clinical trial of new lung cancer drug AXL1717 suggest that the drug effectively treats non-small cell lung cancer (NSCLC). In the study, patients with advanced NSCLC received either AXL1717 or chemotherapy with docetaxel (Taxotere) as a second-line treatment. AXL1717, which works by attacking a protein called IGF1R, appeared to be as effective as Taxotere at delaying cancer progression. AXL1717 may be a treatment option for patients who do not respond or become resistant to Taxotere or other second-line treatments. AXL1717 is manufactured by drug company Axelar. More information about the clinical trial can be found here: http://clinicaltrials.gov/show/NCT01561456
Using a panel of non-small cell lung cancer (NSCLC) lines, we show here that MEK and RAF inhibitors are selectively toxic for the KRAS mutant genotype, while PI 3-kinase (PI3K), AKT and mTOR inhibitors are not. Coordinate direct input of both KRAS and IGF1R is required to activate PI3K in KRAS mutant lung cancer cells.