HER2 receptor is overexpressed approximately in 20 % of human breast cancer (BC) and is a poor prognostic factor. Although therapies targeting this receptor have improved the prognosis of this cancer, up to 62 % patients treated with these drugs experiment progression during the first year of treatment. Some molecular mechanisms have been proposed to be responsible for this resistance, such as activation of alternative signaling pathways (through ERBB receptors and non-ERBB receptors or increased expression of ligands and alterations in HER2 signaling components). In this article, we will review the influence of genetic markers in non-HER2 signaling pathways investigated to date as cause of resistance to HER2-targeted drugs in HER2-positive BC patients. GRB7, included in the 17q12 amplicon, has been associated to poor prognosis in BC patients. Biomarkers like EPHAR and SRC, have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. Non-invasive biomarkers, such as elevated IGF1 serum levels have been revealed as interesting biomarkers to be considered as predictors of trastuzumab clinical outcomes in BC patients. However, the prognostic value of most of the biomarkers investigated to date, such as HER3, IGF1R, PIK3CA, or AKT1 cannot be fully established yet, since results have not been conclusive.
The ABCB1 gene encodes the P-glycoprotein, an efflux pump for some antineoplastic agents which acts as a resistance mechanism to chemotherapy. Three SNPs (C3435T, C1236T and G2677T/A), are the most widely studied in ABCB1. The inconsistent conclusions about the association of these polymorphisms and the response to chemotherapy in breast cancer (BC) patients prompted us to conduct a meta-analysis. A total of nine (770 patients), five (566 patients) and three studies (367 patients) relating the ABCB1 C3435T, C1236T and G2677T/A polymorphisms respectively, were included. The main analysis revealed a lack of association between ABCB1 polymorphisms and response to chemotherapy in every genetic model: C3435T (dominant OR: 0.888; 95%CI: 0.558-1.413), C1236T (dominant OR: 1.968; 95%CI: 0.609-6.362) and G2677T/A (GG vs GT + GA + TT + TA + AA OR: 0.854; 95%CI: 0.418-1.744). Stratification by ethnicity, cancer type and response criteria did not change the pattern of results. The available evidence indicates that three polymorphisms within ABCB1; C3435T, C1236T and G2677T/A, cannot be considered a reliable predictor of response to chemotherapy in BC patients.
Rheumatoid arthritis (RA) is an inflammatory disorder characterized by an aberrant activation of innate and adaptive immune cells. There are different drugs used for the management of RA, including disease-modifying antirheumatic drugs (DMARDs). However, a significant percentage of RA patients do not initially respond to DMARDs. This interindividual variation in drug response is caused by a combination of environmental, genetic and epigenetic factors. In this sense, recent -omic studies have evidenced different molecular signatures involved in this lack of response. The aim of this review is to provide an updated overview of the potential role of -omic approaches, specifically genomics, epigenomics, transcriptomics, and proteomics, to identify molecular biomarkers to predict the clinical efficacy of therapies currently used in this disorder. Despite the great effort carried out in recent years, to date, there are still no validated biomarkers of response to the drugs currently used in RA. -Omic studies have evidenced significant differences in the molecular profiles associated with treatment response for the different drugs used in RA as well as for different cell types. Therefore, global and cell type-specific -omic studies analyzing response to the complete therapeutical arsenal used in RA, including less studied therapies, such as sarilumab and JAK inhibitors, are greatly needed.
Therapies targeting HER2 receptor, overexpressed in 20% breast cancer (BC), improved prognosis, however ~62% patients experiment progression during the first year. Molecular mechanisms proposed to be responsible for this de novo resistance include HER2 modifications, defects in the antibody dependent cellular cytotoxicity or in cell arrest and apoptosis or alterations in HER2 signaling components. This article will review the influence of genetic markers investigated to date as cause of de novo resistance to HER2-targeted drugs in HER2-positive BC patients. Biomarkers like p95HER2, CCND1 and CDC25A have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. However, the prognostic value of most biomarkers investigated to date, such as PIK3CA or AKT1, cannot be fully established yet.
Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Several ABCB1 and VEGFA gene polymorphisms, such as ABCB1-G1199T/A
Background Home Enteral Nutrition (HEN) is used to prevent or correct malnutrition in outpatients. Due to the complexity of this process, the indication, follow-up, and results of an educational program of HEN patients was evaluated. Methods A prospective, observational, real-life, multicenter study was performed in 21 Spanish Hospital. Patients receiving HEN by nasogastric tube or ostomy were included. The following variables were collected: age, gender, HEN indication, type of formula, nutritional requirements, laboratory variables, complications, and quality standards of the educational program. To calculate the energy and protein requirements, the FAO/WHO/UNU formula was used considering the adjusted weight of the patients. All data were analyzed using SPSS.24. Results 414 patients were included. Most conditions diagnosed were neurodegenerative diseases (64.8%). 100 (25.3%) were diabetic. The mean weight was 59.3 ± 10.4 kg and BMI 22.6 ± 3.2. Moderate protein-calorie malnutrition was predominant at baseline (46.4%). Improvement in nutritional status at six months was recorded in more than 75% of patients (p < 0.05). Tolerance problems, diarrhea and abdominal distension fell between the 3- and 6-month visits (p < 0.05). Patients who received intermittent EN had fewer tolerance-related effects (OR 0.042; 95% CI 0.006–0.279) and less diarrhoea (OR 0.042; 95% CI 0.006–0.279). At the baseline and 6-month visits, compliance with the educational measures proposed by the prescriber was ≥ 99%. Conclusion The nutritional assessment to prescribe individualized HEN to each patient, together with educational measures and training in the proper use of this treatment for both patients and trainers, improves nutritional status and reduces the onset of adverse events.
BackgroundVascular endothelial growth factor A (VEGFA) is essential in tumour angiogenesis, and polymorphisms in the VEGFA gene have been associated with breast cancer (BC) prognosis in previously published studies.PurposeTo determine if VEGFA 2578 C >A polymorphism is associated with exitus in HER2 positive BC patients treated with trastuzumab.Material and methodsHER2 positive BC patients, aged ≥18 years with a follow-up period >12 months were included. The duration of the study was from the diagnosis of BC to the time of the patient’s death or the last follow-up.Clinical and histopathological data were collected from the electronic history: exitus date, age, nulliparity, family history of BC, lymph node involvement, oestrogen and progesterone receptor expression, Ki67 antigen, p53 oncogene, stage of the disease, tumour size, grade and histological type, and prescribed treatments.Samples were provided by the local hospital biobank. DNA was extracted using the QIAamp DNA Mini Kit (Qiagen GmBH, Hilden, Germany) according to the manufacturer’s instructions from normal paraffin embedded tissue. Gene polymorphism VEGFA 2578 C >A was analysed by real time PCR using TaqMan probes.Results80 patients were included. 28 patients (28/80; 35.0%) died during the study. Neither clinical nor histopathological factors were associated with exitus. Allelic distribution of the patients was: genotype AA (15/80; 18.75%), AC (37/80; 46.25%) and CC (28/80; 35.0%). Patients carrying the C allele (AC+CC) lived less years than patients with genotype AA.Multivariate logistic regression analysis revealed that VEGFA 2578 C >A AC genotype was a statistically significant factor associated with exitus in HER2 positive patients (OR 0.169, 95% CI 0.04 to 0.67; p = 0.0137).ConclusionThe C allele of the polymorphism VEGFA rs 2578 C >A was associated with exitus in HER2 positive BC patients treated with trastuzumab.No conflict of interest.
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