title: Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.
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.
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez Del Pulgar
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Cebrián
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Fernández-Aceñero
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Aurea
authors.initials: A
authors.lastname: Borrero-Palacios
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Puerto-Nevado
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Useros
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Marín-Arango
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Caramés
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vega-Bravo
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Remírez
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Marlid
authors.initials: M
authors.lastname: Cruz-Ramos
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Manzarbeitia
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000328:Adult; D059248:Chemoradiotherapy; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: chemoradiotherapy; focal adhesion kinase; neoadjuvant therapy; predictive marker; rectal cancer; risk factor