109P - ALK activates ERK5, in both neuroblastoma and lung cancer – a putative therapeutic target in cancer treatment

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Central Nervous System Malignancies
Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Ganesh Umapathy
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors G. Umapathy
  • Medical Biochemistry And Cell Biology, The Sahlgrenska Academy at Gothenburg University, 41390 - Gothenburg/SE

Abstract

Background

ALK, a receptor tyrosine kinase, has been identified as one partner in a wide variety of translocation events which mediate an oncogenic response in different cancer types. A number of small tyrosine kinase inhibitors (TKIs) have been developed that act to inhibit ALK activity, the most studied of these being crizotinib, a small competitive ATP-binding inhibitor currently in clinical use in the treatment of ALK positive NSCLC patients. Initial treatment of ALK+ neuroblastoma patients treated with crizotinib has not provided as clear cut responses as those observed in other cancer types, whereas with ALK+ NSCLC patients it acquires resistance to crizotinib. The data accumulated thus far suggests that monotherapy may not be the solution for all ALK+ neuroblastoma and NSCLC patients, and that individualized combinations of specific drugs might be a future solution to address the disease.

Methods

Xenograft tumor models, western blotting, proliferation assay using resazurin, cell lines used ALK and EGFR positive NSCLC cells.

Results

ERK5, a.k.a. BMK1, is suggested to play a vital role in proliferation, differentiation, and survival. Previously, we have shown that ERK5 activated by ALK through the pathway PI3K/Akt/PKB/MEKK3, which contributes to cell growth of neuroblastoma cell lines. Pharmacological inhibition or siRNA of ERK5 results in decrease in growth of NSCLC cell lines, whereas in combination with ALK inhibitor seems to be more effective both in vitro and in vivo.

Conclusions

Taken together, our results indicate that ERK5 plays an important role in ALK and EGFR positive NSCLC cases, suggesting that targeting ERK5 might be a potential therapeutic target worthy of future exploration for NSCLC patients.

Clinical trial identification

Legal entity responsible for the study

Bengt Hallberg

Funding

Cancerfonden

Disclosure

All authors have declared no conflicts of interest.