Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

Teresa Gómez Del Pulgar,Javier Martínez‐Useros,Marlid Cruz‐Ramos,Juan Pablo Marín‐Arango,Jesús García‐Foncillas,María Rodríguez‐Remírez,Arancha Cebrián,Félix Manzarbeitia,Aurea Borrero‐Palacios,Laura Del Puerto‐Nevado,Maria Jesús Fernández‐Aceñero,Cristina Caramés,Ricardo Vega‐Bravo

doi:10.1111/jcmm.12879

Abstract

Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio‐ and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre‐treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease‐free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence.

Highlights

Rectal cancer represents about 30% of colorectal cancers [1], remaining a significant problem worldwide
It has been found that overexpression of integrin b1, accompanied by increase in cell adhesion and migration through Focal adhesion kinase (FAK)–AKT signalling, is associated with gefitinib resistance in a nonsmall cell lung cancer cell line [15]. These results suggest a possible role of FAK in cancer radio- and chemosensitivity
Evaluation of tumour response to pre-operative CRT showed that 9 patients (12%) had a complete response and 27 (36%) had only isolated tumour cells, all these patients were considered as responders

Summary

Introduction

Rectal cancer represents about 30% of colorectal cancers [1], remaining a significant problem worldwide. In the majority of cases the disease is localized to the primary site with no evidence of distant spread, and in these patients surgical resection currently remains the cornerstone of treatment. Pre-operative chemoradiation (CRT) and total mesorectal excision is currently the standard of care for locally advanced stages of rectal cancer, to reduce the probability of. While complete response is only observed in 10–30% of cases, in the rest of the cases the residual disease varies from microscopic tumour foci to no response at all [7]. Many factors may predict tumour response to CRT [8–12] but up to now, a model that would predict clinically or pathologically complete or partial tumour response after CRT is not available.

Objectives

Methods

Results

Conclusion