Insulin Growth Factor Signaling is Regulated by MicroRNA-486, an Underexpressed MicroRNA in Lung Cancer

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.


Coordinate Direct Input of Both KRAS and IGF1 Receptor to Activation of PI3 kinase in KRAS-Mutant Lung Cancer

“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.”


Study Shows New Drug is Effective against NSCLC

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


Coordinate direct input of both KRAS and IGF1 receptor to activation of PI 3-kinase in KRAS mutant lung cancer

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.


Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf


Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html