Barcelona, May 2015 - Expert investigators from the Dr Rosell Oncology Institute will present results of their investigations into novel methods of detecting genetic alterations and monitoring treatment response in blood from cancer patients. Also to be revealed at the congress are discoveries relating to new predictive biomarkers of response to targeted cancer drugs. Despite advances in recent years with the use of targeted therapies, lung cancer remains one of the most difficult cancers to treat and prognosis for many patients is still poor. Therefore, research efforts focused on advancing understanding of the causes of and treatments for this deadly disease.

EML4-ALK rearrangement in blood platelets and outcome to crizotinib in non-small-cell lung cancer patients

In collaboration with researchers from the Netherlands, the IOR team led by Dr Rafael Rosell has demonstrated how a rearrangement in the EML4-ALK genes which drives tumor growth can be detected in blood samples from advanced non-small-cell lung cancer (NSCLC) patients. By monitoring EML4-ALK in blood platelets, researchers were able to predict outcomes to targeted therapy with the ALK inhibitor Xalkori® and, in one patient, detect drug resistance two months before this was visible by traditional methods such as radiographic imaging. 



ROS1 rearrangement in non-small cell lung cancer (NSCLC): Prognostic and predictive impact and genetic variability

In collaboration with the Cologne Lung Cancer Group, investigators found that rearrangements in the ROS1 gene which drive lung cancer can be used as a prognostic biomarker to select patients most likely to benefit from targeted therapy with the ROS1 inhibitor Xalkori®. It was observed that ROS1-positive patients responded better to therapy and had longer survival than other groups of patients analyzed. Based on the results of the study, the investigators concluded that ROS1 may be the strongest biomarker found to date for advanced NSCLC. 



BIM and SHP2 expression levels predict clinical outcome to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients

For this study, investigators measured mRNA levels of the BIM and SHP2 genes in NSCLC patients with mutations in the epidermal growth factor receptor (EGFR) gene who had been treated with inhibitors of EGFR. The findings were correlated with progression-free (PFS) and overall survival (OS). High levels of BIM mRNA emerged as a predictive marker of response to therapy, PFS and OS in these patients, reinforcing the potential of BIM mRNA as a predictive biomarker for response to treatment with EGFR inhibitors.



Serial mutational analysis to monitor disease evolution in blood from advanced non-small-cell lung cancer (NSCLC) patients

“Liquid biopsies” can provide a useful alternative to traditional tissue biopsies in cases where sufficient tumor tissue for genetic analyses is unavailable. IOR investigators have developed a sensitive assay to detect mutations in the EGFR, KRAS and BRAF genes in cell-free DNA (cfDNA) from serum and plasma from blood from advanced NSCLC patients. Results of the assay were compared with clinical and radiological evolution of the disease and, based on the findings, the researchers concluded that serial analyses of EGFR and KRAS mutations in cfDNA from these patients constitutes a novel, non-invasive method to monitor disease progression in real-time.

Analysis of gene expression in the re-replication pathway and selective blockade with checkpoint inhibitors as a potential therapeutic option in NSCLC

Genome re-replication is a potential cause of tumor growth, therefore the ability to control this process could be crucial to halting cancer progression. In this study, investigators discovered that high levels of activity of certain genes involved in the DNA re-replication process makes them potential targets for therapy. In addition, cell cycle checkpoints - control mechanisms which ensure proper cell division - such as CHK-1 are activated when DNA re-replication is induced. Researchers were able to successfully inhibit growth of some NSCLC cells in the lab by treating them with LY2603618, a drug that inhibits CHK-1.

Results will be presented at the congress in the form of posters or published in the abstract book.