Abstract. pre-operative chemoradiotherapy (crt) is an important neoadjuvant therapy for locally advanced rectal cancer. in the present study, we investigated the factors that influence the efficacy of pre-operative CRT in locally advanced rectal cancer. We divided 50 patients with locally advanced rectal carcinoma treated with pre-operative crt into two groups according to the grade of tumor response to pre-operative crt: low-sensitivity group and high-sensitivity group. as candidates for the prediction of sensitivity to preoperative crt, clinicopathological factors and 12 biomarkers, including factors related to tumor growth, cell cycle, apoptosis, tumor stroma and cancer stem cells, were examined immunohistochemically in 48 resected specimens. thirty-one tumors showed high sensitivity and 19 showed low sensitivity to pre-operative crt. the status of stem cell-related factors, CD133 and CD24, was significantly associated respectively with sensitivity to pre-operative crt (p=0.003, p=0.029). in 10 tumors positive for both cd133 and cd24, low sensitivity to crt was found in 9 (90%), whereas in 16 tumors negative for both cd133 and cd24, low sensitivity was found in 3 (19%). Other pathological parameters were not associated with tumor response to pre-operative crt. in conclusion, overexpression of cancer stem cell-related factors, cd133 and cd24, is associated with the sensitivity of locally advanced rectal cancer to pre-operative crt.Introduction colorectal cancer is a leading cause of morbidity and mortality in developed countries (1). in Japan, an increasingly Westernized diet has led to a high incidence of colorectal cancer. patients with rectal cancers are known to have an increased rate of local recurrence and decreased survival time compared to patients with tumors of the colon, a result due primarily to the surgical constraints imposed by the location of the rectum within the pelvis (2).pre-operative chemoradiotherapy (crt) is a neoadjuvant therapy for locally advanced rectal cancer that reduces the incidence of local recurrence and improves survival (3). therefore, crt is widely used in many countries of the world. however, several tumors show a marked response to crt, whereas others do not. Furthermore, several adverse events related to crt, such as enteritis, anorexia, cardiac/ thromboembolic events, radiation dermatitis and hematologic toxicity, were reported to occur at frequencies of 6-43% (4). thus, pre-operative indicators of chemoradiosensitivity are required to avoid unnecessary application of pre-operative crt, yet little is known about potential biological markers that may be associated with response to pre-operative crt.recently, the discovery of rare subpopulations of cancer stem cells has created a new focus in cancer research. the heterogeneity of tumors can be explained by the concept of cancer stem cells supported by anti-apoptotic signaling. there are a few reports on cancer stem cells related to chemoradiation resistance (5,6). therefore, in this study we investigated the factors, inclu...