Pernia O.,Hospital Universitario La Paz |
Belda-Iniesta C.,Biomarkers and Experimental Therapeutics in Cancer |
Belda-Iniesta C.,University Hospital Madrid Norte Sanchinarro |
Pulido V.,Hospital Universitario La Paz |
And 17 more authors.
Epigenetics | Year: 2014
The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p =.03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter. © 2014 Taylor & Francis Group, LLC.
PubMed | Biomarkers and Experimental Therapeutics in Cancer and Hospital Universitario La Paz
Type: | Journal: Translational research : the journal of laboratory and clinical medicine | Year: 2016
Epigenetics is currently in an exponential phase of growth, constituting one of the most promising fields in science, particularly in cancer research. Impaired epigenetic processes can lead to abnormal gene activity or inactivity, causing cellular disorders that are closely associated with tumor initiation and progression. Thus, there is a pivotal role of massive sequencing techniques for epigenetics, which aim to find novel biomarkers, factors of prognosis and prediction, and targets for achieving personalized treatments. We present a brief description of the evolution of next-generation sequencing technologies and its coupling with DNA methylation analysis techniques, highlighting its future in translational medicine and presenting significant findings in several malignancies. We also expose critical topics related to the implementation of these approaches, which is expected to be affordable for most research centers in the near future.