Potential crosstalk between cofilin-1 and EGFR pathways in cisplatin resistance of non-small-cell lung cancer.

Carolina Beatriz Müller,Fernanda Stapenhorst França,Matheus Becker,Mauro Antônio Alves Castro,Mariane Araujo Branco,Marco Antônio De Bastiani,Fábio Klamt

doi:10.18632/oncotarget.3471

Abstract

Current challenge in oncology is to establish the concept of personalized medicine in clinical practice. In this context, non-small-cell lung cancer (NSCLC) presents clinical, histological and molecular heterogeneity, being one of the most genomically diverse of all cancers. Recent advances added Epidermal Growth Factor Receptor (EGFR) as a predictive biomarker for patients with advanced NSCLC. In tumors with activating EGFR mutations, tyrosine kinase inhibitors (TKI) are indicated as first-line treatment, although restricted to a very small target population. In this context, cofilin-1 (a cytosolic protein involved with actin dynamics) has been widely studied as a biomarker of an aggressive phenotype in tumors, and overexpression of cofilin-1 is associated with cisplatin resistance and poor prognosis in NSCLC. Here, we gather information about the predictive potential of cofilin-1 and reviewed the crosstalk between cofilin-1/EGFR pathways. We aimed to highlight new perspectives of how these interactions might affect cisplatin resistance in NSCLC. We propose that cofilin-1 quantification in clinical samples in combination with presence/absence of EGFR mutation could be used to select patients that would benefit from TKI's treatment. This information is of paramount importance and could result in a possibility of guiding more effective treatments to NSCLC patients.

Highlights

The current challenge in oncology is to establish the concept of personalized medicine in clinical practice [1]
Considering the information gathered here, it seems clear that cofilin-1 regulation and functions are closely related to Epidermal Growth Factor Receptor (EGFR) activity
EGFR functions inside the nucleus have been subject of intense study, leading to many possible roles of its translocation upon several stimuli [77]

Summary

INTRODUCTION

The current challenge in oncology is to establish the concept of personalized medicine in clinical practice [1]. Meta-analysis of other independent cohorts microarray data corroborates that cofilin-1 has a prognostic capability, indicating that patients with higher levels of this protein are more likely to be at the poorer outcome group (Figure 1) In these works, the relation of cofilin-1’s expression with a more aggressive phenotype of tumors was attributed to its classical activity upon actin www.impactjournals.com/oncotarget cytoskeleton modulation, related to improved migration and invasion capacity in cancer cells, as reviewed recently [26]. There www.impactjournals.com/oncotarget are no studies trying to associate nuclear cofilin-1 with patient’s outcome/prognosis in lung cancer

CONCLUSIONS

Findings

CONFLICT OF INTEREST DECLARATION