Radiosensitizing Biological Modifiers Enhancing Efficacy in Non-Small-Cell Lung Cancer Treated with Radiotherapy

Abstract

251 ISSN 1758-1966 10.2217/LMT.13.25 © 2013 Future Medicine Ltd Lung Cancer Manage. (2013) 2(4), 251–255 The leading cause of cancer-related mortality worldwide is lung cancer, with an average 5-year overall survival rate of only 10–15%, taking all clinical stages together [1]. Lung cancer can be divided into two major histological groups: non-small-cell lung cancer (NSCLC) and small-cell lung cancer. NSCLC is the dominating group in Sweden, comprising more than 85% of all newly diagnosed lung cancer patients; the rest of this article will focus on this tumor entity. Treatments for these patients are based on surgery if the tumor has not spread and is technically removable, and these patients display a better 5-year survival [2]. However, many patients present with locally advanced disease (stage IIIb), metastatic disease (stage IV) or comorbidities, rendering less than 20% of the patients medically operable [3]. Thus, curatively intended radiotherapy, alone or in combination with chemotherapy, offers in many cases the only possibility of cure in localized NSCLC. The effect of radiotherapy depends on the absorption of radiation, which occurs by interaction with orbital electrons in the atoms that are being exposed [4]. Radiation produces a variety of damage to macromolecular components by altering DNA and RNA bases and sugars, inducing DNA–protein and DNA–DNA crosslinks and further by inducing singleand doublestrand breaks [5]. However, despite this induced damage, the cell is fully capable of repairing itself by using five major DNA repair systems: nucleotide excision repair [6]; base excision repair [7]; mismatch repair [8]; homologous recombinational repair [9]; and nonhomologous end joining [10]. Unfortunately for patients with NSCLC, these systems are well functioning and NSCLC is considered as a relatively radioresistant tumor. In a retrospective study by Holgersson et al., which was a collaborative effort among all the Swedish oncology departments, clinical data were collected for 1146 patients with diagnosed NSCLC subjected to curatively intended irradiation (>50 Gy) during the years 1990–2000 [11]. Among the 1146 patients with nonsmall-cell carcinoma eligible for ana lysis,