al. re ported overexpression of Aurora A protein in 19% of CRC by immunohistochemistry. High copy amplification of the Aurora A gene was found in colorectal tumors and associated with chromosomal instability phenotypes. In another report, up regulation of Aurora kinases were detected in 48. 5% of patients with colorectal carcinoma. Similarly, a previous study reported that the presence of nuclear Aurora B was strongly associated with lymph node metastasis in colorectal cancer. In metastatic colorectal cancer, patients with a high expres sion level of Aurora B lived significantly shorter compared with patients with a low expression level. Taken to gether, these studies highlight the association of altered aurora kinases and CRC. As far as therapeutic options, 5 Fluorouracil re mains the most commonly used chemotherapeutic agent for CRC.

However, CRC tumors are highly refractory to chemotherapy and many patients eventually relapse. Be cause of the established roles of Aurora kinases in tumor initiation and progression, many inhibitors of Aurora ki nases pop over to this site have been specifically tested for the treatment of colorectal cancers in combination with 5 FU, with some currently in clinical trials. Recent studies showed that overexpression of Aurora kinases might have a role in chemo and radiotherapy resistance of cancers. Consistent with this notion, inhibition of Aurora kinases can enhance radiation sen sitivity of cancer cells. For example, inhibition of Aurora B sensitizes mesothelioma cells by enhancing mitotic arrests and also potently suppresses repopu lation during fractionated irradiation of human lung cancer cell lines.

CCT137690 is a newly synthesized compound informative post which has been shown to inhibit the activities of Aurora ki nases. IC50 values of CCT137690 are 15 and 25 nM for Aurora A and B, respectively. Although CCT137690 has shown promising therapeutic effects on different cancer cells, a narrow safety margin may limit its preclinical development. The main cause of treatment failure and recurrence is resistance of cancer cells to radiation and drugs. Since inhibition of Aurora kinases can sensitize cancer cells to radiotherapy, it is expected that combining radio therapy and Aurora inhibition for colorectal cancers may achieve a synergistic therapeutic effects.

Concomitant in hibition of Aurora kinases and radiotherapy can also potentially decrease the dosages of either medicine or radiation, which in turns can reduce the side effects of the treatments. Therefore, in our current study we sought to explore whether the combination of radio therapy with CCT137690 may prove efficacious in the treatment of colorectal cancer cell lines. In this way, optimized combinatorial treatment may lead to a de crease in the requirement of CCT137690 for thera peutic benefit.