Predicting the tumor response to radiotherapy using microarray analysis (Review)

Abstract

Abstract. Predicting the tumor response to radiotherapy is one of the major goals of human cancer treatment. Identification of the genes that are differentially expressed between radiosensitive and radioresistant cancers by global gene analysis may provide new insights into the mechanisms underlying clinical radioresistance and improve the efficacy of radiotherapy. In this study, we reviewed the published reports identifying sets of discriminating genes using microarray analysis that can be used for characterization and the prediction of response to radiotherapy in human cancers. These reports indicate that many of the identified genes were associated with DNA-repair, apoptosis, growth factor, signal transduction, cell cycle and cell adhesion. Several genes were found to be predictors of the radiation response with various cancers and certain sets of identified genes were also found to predict the radiation response by using clustering analysis. Global gene expression profiling of responders and nonresponders can be useful in predicting responses to radiotherapy and may also provide insights into the development of individualized therapies and novel therapeutic targets. Contents1. Introduction 2. Microarray analysis comparing radiosensitive and radioresistant cancer samples and cancer cell lines 3. Summary of the identified genes from cancer cell lines investigated by microarray IntroductionRadiotherapy is one of the major treatments for patients with various cancers. The general rationale for radiotherapy is based on the findings that radiation can inhibit cell proliferation or induce apoptotic cell death in vitro and inhibit tumor growth in vivo (1). However, the tumor response to radiotherapy sometimes differs among individual tumors even with the same histological field, and the lack of knowledge regarding the determinants of response has handicapped the development of predictive assays and the development of novel treatment strategies. Therefore, identification of the determinants of the tumor response to radiation has long been a goal of radiation oncologists and biologists. Recently, an association between radioresistance and the expression of several genes was observed, with candidate genes, such as p53 (2), ras (3), raf-1 (4), bcl-2 (5) and survivin (6). Furthermore, cancer stem cells have emerged as a contributor to radioresistance through the preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity (7). Although such discoveries have helped develop a partial understanding of the molecular mechanisms responsible for cellular radiosensitivity, the entire process remains to be elucidated. The advent of microarray gene expression technology permits simultaneous analysis of the expression levels of thousands of genes (8-10). Therefore, a study on molecular genetic events related to radiosensitivity can be conducted. This research can lead to the identification of gene regulatory pathways that result in the development of resistance to therapeutic procedures. To d...

High expression of mTOR is associated with radiation resistance in cervical cancer

“…Identification of molecular biomarkers associated with the prognosis of patients with cervical cancer may help devise new treatment strategies to improve the clinical outcome of radioresistant cancer in patients. Ogawa et al 3 reviewed the published reports describing microarray analysis to identify sets of genes that can be used for the characterization and prediction of response to radiotherapy in human cancers. These reports indicate that genes linked to cervical cancer are associated with DNA repair (XRCC5), apoptosis (BIK, SSI-3), signal transduction (MAP3K2: mitogen-activated protein kinase pathway), invasion and metastasis (CTSL, PLAU), hypoxia (HIF1A, CA12), and other functions (e.g., ALDH1).…”

Enhancing radiosensitivity: Targeting the DNA repair pathways

“…58,59 This area of research is sadly lagging and needs to be developed much further if pathway specific targeting is to reach its full potential. If tumor genotyping or DNA pathway specific biomarkers were to become available, however, it would allow us to stratify patients for therapies to identify the subsets that could benefit from a DNA repair targeted approach.…”

Bioinformatics of Treatment Response

“…These biomarkers can be further divided into single parameter (e.g., prostate-specific antigen (PSA) levels in blood serum) versus bio-arrays. These can be based on disease pathophysiology or pharmacogenetic studies or they can be extracted from several methods, such as high-throughput gene expression (aka transcriptomics) [44][45][46], resulting protein expressions (aka proteomics) [47,48], or metabolites (aka metabolomics) [49,50]. On the other hand, the inherent genetic variability of the human genome is an emerging resource for studying disposition to cancer and the variability of patient responses to therapeutic agents.…”