Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

An overview of resistance to chemotherapy in osteosarcoma and future perspectives.

Osteosarcoma (OS) is the most common type of bone sarcoma. Despite the availability of multimodal treatment with surgery and chemotherapy, the clinical results remain unsatisfactory. The main reason for the poor outcomes in patients with OS is the development of resistance to methotrexate, cisplatin, doxorubicin, and ifosfamide. Molecular and cellular mechanisms associated with resistance to chemotherapy include DNA repair and cell-cycle alterations, enhanced drug efflux, increased detoxification, resistance to apoptosis, autophagy, tumor extracellular matrix, and angiogenesis. This versatility of cells to generate chemoresistance has motivated the use of anti-angiogenic therapy based on tyrosine kinase inhibitors. This approach has shown that other therapies, along with standard chemotherapy, can improve responses to therapy in patients with OS. Moreover, microRNAs may act as predictors of drug resistance in OS. This review provides insight into the molecular and cellular mechanisms involved in the development of resistance during the treatment of OS and discusses promising novel therapies (e.g., afatinib and palbociclib) for overcoming resistance to chemotherapy in OS.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Factor structure, internal consistency and distribution of Female Sexual Function Index among Mexican women with early diagnostic of breast cancer / Estructura factorial, consistencia interna y distribución del Índice de Función Sexual Femenina entre mujeres mexicanas con diagnóstico temprano de cáncer de mama

Background: Female Sexual Dysfunction (FSD) occurs frequently in women with breast cancer due to oncologic treatments. It is essential to have a validated instrument to diagnose and quantify FSD in this population accurately. Objective: To validate the Female Sexual Function Index (FSFI). Method: The FSFI was applied to 272 sexually active Mexican women with recent diagnosis of breast cancer who had not initiated systemic cancer treatment. Results: The FSFI six-factor model is valid by confirmatory factor analysis, and the inventory and its factors have adequate internal consistency reliability. Conclusions: This study provides enough evidence about the reliability and factor structure of the FSFI questionnaire in the context of breast cancer clinical practice in Mexico (AU)

Antecedentes: La disfunción sexual femenina (FSD) ocurre con frecuencia en mujeres con cáncer de mama debido a los tratamientos oncológicos. Es fundamental contar con un instrumento validado para diagnosticar y cuantificar la FSD en esta población con precisión. Objetivo Validar el Índice de Función Sexual Femenina (FSFI). Método: El FSFI se aplicó a 272 mujeres mexicanas sexualmente activas con diagnóstico reciente de cáncer de mama que no habían iniciado tratamiento oncológico sistémico. Resultados: El modelo de seis factores de la FSFI se validó por análisis factorial confirmatorio y el inventario y sus factores tienen una fiabilidad de consistencia interna adecuada. Conclusiones: Este estudio proporciona suficiente evidencia sobre la confiabilidad y la estructura factorial del cuestionario FSFI en el contexto de la práctica clínica del cáncer de mama en México (AU)

Prospective Study of Fertility Preservation in Young Women With Breast Cancer in Mexico.

BACKGROUND: Despite the risk of treatment-related infertility, implementation of fertility-preservation (FP) strategies among young patients with breast cancer is often suboptimal in resource-constrained settings such as Mexico. The "Joven & Fuerte: Program for Young Women With Breast Cancer" strives to enhance patient access to supportive care services, including FP measures through alliances with assisted-reproduction units and procurement of coverage of some of these strategies. This study describes patients from Joven & Fuerte who have preserved fertility, and assesses which characteristics were associated with the likelihood of undergoing FP. METHODS: Women aged ≤40 years with recently diagnosed breast cancer were prospectively accrued. Sociodemographic and clinicopathologic data were collected from patient-reported and provider-recorded information at diagnosis and 1-year follow-up. Descriptive statistics, chi-square test, and simple logistic regression were used to compare patients who preserved fertility with those who did not. RESULTS: In total, 447 patients were included, among which 53 (12%) preserved fertility, representing 38% of the 140 women who desired future biologic children. Oocyte/embryo cryopreservation was the most frequently used method for FP (59%), followed by temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy (26%), and use of both GnRHa and oocyte/embryo cryopreservation (15%). Younger age, higher educational level, being employed, having private healthcare insurance, and having one or no children were associated with a significantly higher likelihood of preserving fertility. CONCLUSIONS: By facilitating referral and seeking funds and special discounts for underserved patients, supportive care programs for young women with breast cancer can play a crucial role on enhancing access to oncofertility services that would otherwise be prohibitive because of their high costs, particularly in resource-constrained settings. For these efforts to be successful and widely applied in the long term, sustained and extended governmental coverage of FP options for this young group is warranted.

Adjuvant endocrine therapy for premenopausal women with breast cancer: Patient adherence and physician prescribing practices in Mexico.

BACKGROUND: In resource-constrained settings, data regarding breast cancer patients' adherence to endocrine therapy (ET) and physicians' prescribing practices is limited. This study aims to decrease this knowledge gap in a real-world clinical practice. METHODS: Premenopausal women with stage 0-III hormone-sensitive breast cancer and receiving adjuvant ET during the past 1-5 years were identified in three Mexican referral centers. Participants' self-reported ET compliance, clinicopathologic characteristics, ET-related knowledge and beliefs, experienced adverse effects, social support, and patient-physician relationships were evaluated. Physician ET prescribing practices were compared with the gold standard according to international and national guidelines to assess clinicians' adherence to standard-of-care prescription. RESULTS: In total, 95/132 (72%) and 35/132 (27%) participants reported complete and acceptable adherence, respectively. Incomplete adherence was mainly attributed to forgetfulness, adverse effects, and unwillingness to take ET. Being employed/studying (p = 0.042), worrying about long-term ET use (p = 0.031), and experiencing >7 ET-related symptoms (p = 0.018) were associated with incomplete adherence. Guideline-endorsed regimens were prescribed in 84/132 (64%) patients, while the rest should have undergone ovarian function suppression (OFS) but instead received tamoxifen monotherapy. CONCLUSIONS: Premenopausal Mexican women self-report remarkably high rates of adequate ET adherence. However, a considerable proportion misses ≥1 doses/month, usually because of forgetfulness. Notably, only 64% receive standard-of-care ET due to suboptimal prescription of OFS. Interventions that remind patients to take their ET, refine physicians' knowledge on the importance of OFS in high-risk patients, and increase access to OFS could prove pivotal to enhance optimal ET implementation and adherence, which could translate into improved patient outcomes.

Improving Collection of Real-World Data: The Experience of the Joven & Fuerte Prospective Cohort for Mexican Young Women With Breast Cancer.

The prospective collection of clinical data can generate detailed information on heterogeneous populations. This article reviews the strengths and limitations of the collection of real-world data and provides insight into the feasibility of routine collection of high-quality evidence even in a resource-constrained setting. The acquisition of high-quality data to assess the clinical and psychosocial needs of young Mexican patients with breast cancer has been enhanced through the use of preplanned, standardized data definitions and instrumentation to provide internally and externally comparable results, optimization of data collection with web-based surveys, engagement of participants to minimize missing data, and routine review for data consistency. A similar approach by other research groups could improve the quality of real-world data and accomplish enhanced inference of information.

Acellular fraction from malignant effusions has cytotoxicity in breast cancer cells.

Malignant ascites (MA) and malignant pleural effusion (MPE) are frequently developed in patients with metastatic cancer; however, the biological properties of these fluids have not been clarified. The present study explored the biological role of a low molecular fraction derived from malignant effusions on the activation of peripheral blood mononuclear cells and on the proliferation of breast cancer cells and fibroblast 55x cells. A <10-kDa fraction from effusions of 41 oncological patients and 34 individuals without cancer was purified, and its potential role in inhibiting nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells was explored, as well as its cytotoxicity on MCF-7 breast cancer cells and fibroblast 55x cells. A significant decrease in NO production was observed in the <10-kDa fraction from malignant effusions. In addition, the acellular fraction from MA decreased the viability of breast cancer cells without affecting human fibroblasts. These data support the presence of low molecular weight molecules in malignant samples with a specific role in inhibiting the defense mechanisms of peripheral blood mononuclear cells and decreasing the viability of breast cancer cells in vitro.

Targeting Galectin-1 by Aflibercept Strongly Enhances Its Antitumor Effect in Neuroendocrine Carcinomas.

BACKGROUND: Galectin-1 (Gal-1) plays major roles in cancer by modulating different processes leading to tumor development and progression. In the last years, it has been suggested as a promising target for anticancer therapy. Recently, aflibercept has shown high affinity for Gal-1. Here, we investigated how aflibercept could exert its antitumor activity via Gal-1-driven pathways in neuroendocrine carcinomas (NECs). METHODS AND RESULTS: NEC tumor xenografts were used to assess the effect of aflibercept on Gal-1 functions. Aflibercept induced a significant reduction of Gal-1 at epithelial, stromal, and extracellular localizations in lung NEC, whereas this was not observed in colon NECs, which displayed low expression of Gal-1. Additionally, aflibercept significantly reduced p-VEGFR2 protein, extracellular matrix remodeling, epithelial-mesenchymal transition, and activation of cancer-associated fibroblast hampering cell invasion in lung NEC but not in colon NEC. Gal-1 screening in human NECs confirmed that pulmonary and pancreatic tumors displayed higher levels of Gal-1 than colon NECs, becoming good candidates to benefit from aflibercept treatment. CONCLUSIONS: The lack of validated predictive markers of aflibercept is a weakness for guaranteeing the best treatment management with this drug. This work provides new mechanistic insight of aflibercept depending on Gal-1. Thus, in tumors overexpressing Gal-1, aflibercept has not only an antiangiogenic effect but also prevents Gal-1-mediated tumor-stroma cross talk. The stronger aflibercept effect in tumors with high levels of Gal-1 points out this protein as a molecular marker to predict the efficacy of this agent not only for NECs but also for other tumors with high levels of this protein.

Communication Challenges Among Oncologists in Mexico.

Communication challenges related to the delivery of bad news are present in oncologists' daily practice. Hence, communication skills are essential for clinicians to handle these situations as appropriately and compassionately as possible. The aim of this study was to identify Mexican oncologists' perceptions on the most important and hardest issues to discuss with patients and their families, as well as the challenges they most commonly encounter when communicating bad news. Physicians from various oncology centers were invited to anonymously complete an electronical survey designed by our multidisciplinary oncology team. Statistical analysis was performed with the SPSS software v25; descriptive statistics were used for the analysis of the survey's answers. In total, 115 physicians were included; most were medical oncologists. Treatment objectives and prognosis were the topics most of them considered relevant to address; while end-of-life care and treatment objectives were the hardest ones to discuss. The most difficult challenges they faced when breaking bad news were being honest without taking away hope and dealing with patients' emotions. Remarkably, we detected a lack of training in delivering bad news to patients among our participants, as a minority of them had formal training in the matter. However, most desired to receive communication skills training and believed a session of 2-5 h would be sufficient. Mexican oncologists face diverse communication challenges when disclosing bad news to patients. Our findings reveal an opportunity to develop formal training programs tailored for Mexican oncologists and to ultimately improve outcomes and patient-centered care.

NLRP3 Inflammasome: The Stormy Link Between Obesity and COVID-19.

Several countries around the world have faced an important obesity challenge for the past four decades as the result of an obesogenic environment. This disease has a multifactorial origin and it is associated with multiple comorbidities including type 2 diabetes, hypertension, osteoarthritis, metabolic syndrome, cancer, and dyslipidemia. With regard to dyslipidemia, hypertriglyceridemia is a well-known activator of the NLRP3 inflammasome, triggering adipokines and cytokines secretion which in addition induce a systemic inflammatory state that provides an adequate scenario for infections, particularly those mediated by viruses such as HIV, H1N1 influenza, and SARS-CoV-2. The SARS-CoV-2 infection causes the coronavirus disease 2019 (COVID-19) and it is responsible for the pandemic that we are currently living. COVID-19 causes an aggressive immune response known as cytokine release syndrome or cytokine storm that causes multiorgan failure and in most cases leads to death. In the present work, we aimed to review the molecular mechanisms by which obesity-associated systemic inflammation could cause a more severe clinical presentation of COVID-19. The SARS-CoV-2 infection could potentiate or accelerate the pre-existing systemic inflammatory state of individuals with obesity, via the NLRP3 inflammasome activation and the release of pro-inflammatory cytokines from cells trough Gasdermin-pores commonly found in cell death by pyroptosis.

Correction to: Afatinib is active in osteosarcoma cell lines.

The title of the article is incorrectly published in the original article. The correct article title is "Afatinib is active in osteosarcoma cell lines".

Afatinib is active in osteosarcoma in osteosarcoma cell lines.

PURPOSE: Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. Preclinical and clinical studies have suggested a possible important role of ErbB pathway aberrations in osteosarcoma etiology. The present study shows the effect of afatinib, an irreversible ErbB family blocker in osteosarcoma cell lines. METHODS: Within a panel of human osteosarcoma cell lines, we addressed cell viability assay using afatinib at increasing concentrations. Motility was measured in wound-healing assays and invasion capacity was assessed in Transwell chamber assays. Finally, to monitor ErbB pathway modulation by afatinib and related compounds, we used Western blot analyses. RESULTS: Cell viability inhibition, as well as a reduction of motility and migration of osteosarcoma cell line were observed after treatment with afatinib. Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. CONCLUSIONS: Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.

Patients' satisfaction with a supportive care program for young breast cancer patients in Mexico: Joven & Fuerte supports patients' needs and eases their illness process.

OBJECTIVE: The aim of this study was to evaluate patients' outlook and satisfaction with "Joven & Fuerte: Program for Young Women with Breast Cancer (YWBC) in Mexico" (J&F) and to determine its strengths and areas of improvement to better fulfill patients' information and supportive care needs. METHODS: Patients enrolled in J&F for ≥ 6 months at three cancer referral centers were invited via a messaging application to anonymously complete an online survey exploring their perspectives of the program's information delivery, support services, and research component. Descriptive statistics, chi2 test, Student t, and ANOVA were used for analysis. RESULTS: Of 484 eligible patients, 28% completed the survey. The program overall was useful/very useful according to 97% and aided 82% to better cope with their illness. The timing, clarity, and usefulness of the information provided were each described as good/very good by ≥ 83% for the written format and ≥ 98% for the verbal one. Eighty-four percent of patients were very satisfied (≥ 9/10) with psychological support and genetic assessment. The number of support services used was significantly associated with patients' perception of J&F's usefulness. Regarding fertility issues, 45% recalled being informed about preservation strategies and J&F financially supported 27/39 of interested patients. Fifty-eight percent were unaware of J&F's ongoing research component. CONCLUSIONS: Patients' satisfaction with J&F is very high, reflecting that the program is meeting Mexican YWBC's needs by providing useful information means and support services in a limited-resource setting. Efforts must keep up to guarantee the program's continuity and advocate for its extension to other oncologic centers.

Strong Antitumor Activity of Bevacizumab and Aflibercept in Neuroendocrine Carcinomas: In-Depth Preclinical Study.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare and very aggressive tumor. It has been greatly understudied, and very little is known about optimal treatment strategy for patients with this disease. The purpose of this study was to evaluate in vivo whether anti-vascular endothelial growth factor (VEGF) drugs could be a therapeutic alternative for these tumors with a poor prognosis. METHODS: We have developed 2 xenograft models using either human cell line derived from lung (H460) or from colon (COLO320) NEC to assess the effect of 2 antiangiogenic drugs, aflibercept and bevacizumab, on tumor growth and their pathological characteristics. Additionally, tumors were subjected to immunohistochemistry staining and proteins were measured with Western blot and ELISA. RESULTS: Both aflibercept and bevacizumab showed significant antitumor activity (p < 0.001). In the H460 model, aflibercept resulted in 94% tumor growth inhibition (TGI) and bevacizumab treatment resulted in 72.2% TGI. Similarly, in the COLO320 model, aflibercept and bevacizumab resulted in 89.3 and 84% TGI, respectively. Moreover, antitumor activity occurs early after treatment initiation. Using Tumor Control Index score, which address the kinetics of tumor growth in a way comparable to the methods used in human clinical studies, we confirmed that both drugs inhibit significantly tumor growth. When tumor stabilization was evaluated, aflibercept shows higher ability to stabilize NEC tumors than bevacizumab. CONCLUSION: Results derived from this study strongly support anti-VEGF therapies, especially aflibercept, as a novel therapeutic option in NECs. Further studies are necessary, but our observations encourage the evaluation of antiangiogenics in clinical trials combined with standard chemotherapy.

CAR-T cell and Personalized Medicine.

Adoptive T cell transfer (ACT) is a new era for cancer treatment, involving infusion of autologous lymphocytes. Chimeric antigen receptors (CAR) on the surface of T cells are emerging as a novel therapeutic that is giving other direction to T-cell specificity and precision medicine. T cells are engineered modification to recognize specific target antigen and are co-stimulated with intracellular signal to increase the T cell response. CAR-T cells have impressive involvement in outcome on hematological malignancies; however severe toxicities as cytokine release syndrome or neurotoxicity are a challenge to face. Solid tumors have heterogeneous antigens and tumor microenvironment that hinder CAR-T cell efficacy and increase the risk of on-target/off-tumor. Novel strategies to increase CAR-Ts specificity, safety and efficacy are ongoing in clinical trials to improve clinical outcomes in hematological and solid malignances.

Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to lymphocyte ratio in older patients with metastatic colorectal cancer.

Aging is associated with a higher risk of cancer, >70% of cancer-related deaths occur in aged patients; however, this population is underrepresented in clinical trials, therefore, clinical information regarding this age group is rather limited. OBJECTIVES: Neutrophil-to lymphocyte ratio (NLR) and platelet-to lymphocyte ratio (PLR) have been described as biomarkers in cancer, thus, we have assessed their impact in an aged cohort of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: 110 patients with a mean age of 72.2 years at diagnosis were retrospectively reviewed; NLR and PLR were calculated and dichotomized using a cutoff point estimated by a ROC curve. Survival curves and Cox regression analysis were performed to assess the prognostic potential of ratios in terms of progression free survival (PFS) and overall survival (OS). RESULTS: High NLR was associated to worse outcome in terms of PFS (ten vs sixteen months; Log rank <0.001) (HR 2.00 95%CI 1. 29-3.11; p = .002) and OS (20 vs 26 months; Log rank 0.002) (HR 2.28 95%CI 1.40-3.71; p = .001). Similarly it occurs with high PLR and PFS (nine vs fifteen months; Log rank 0.04) (HR 1.55 95%CI 1.01-2.40; p = .04) and OS (nineteen vs 25 months; Log rank <0.001) (HR 2.35 95%CI 1.45-3.80; p < .001). CONCLUSION: This study confirms the role of NLR and PLR as accessible and noninvasive biomarkers that could be use as a routine tool in the clinical practice in geriatric patients with mCRC.

Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. However, tumor response following NACRT varies, ranging from pathologic complete response to disease progression. We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and as such are potential predictors of tumor response and may aid in identifying patients who could benefit from NACRT. METHODS: Sixty-seven pretreatment biopsies were examined for VRK1 and VRK2 expression using tissue microarrays. VRK1 and VRK2 Histoscores were combined by linear addition, resulting in a new variable designated as "composite score", and the statistical significance of this variable was assessed by univariate and multivariate logistic regression. The Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC) analysis were carried out to evaluate calibration and discrimination, respectively. A nomogram was also developed. RESULTS: Univariate logistic regression showed that tumor size as well as composite score were statistically significant. Both variables remained significant in the multivariate analysis, obtaining an OR for tumor size of 0.65 (95 % CI, 0.45-0.94; p = 0.021) and composite score of 1.24 (95 % CI, 1.07-1.48; p = 0.005). Hosmer-Lemeshow test showed an adequate model calibration (p = 0.630) and good discrimination was also achieved, AUC 0.79 (95 % CI, 0.68-0.90). CONCLUSIONS: This study provides novel data on the role of VRK1 and VRK2 in predicting tumor response to NACRT, and we propose a model with high predictive ability which could have a substantial impact on clinical management of locally advanced rectal cancer.

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

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.