The presence of detectable circulating tumor cells could indicate the presence of disease, aiding diagnosis, and a decline over time could represent a response

to therapy. The simple ability to assess the effects of treatment on an individual patient’s tumor would represent a significant advance in the management of biliary system tumors. An embarrassing truth is Inhibitors,research,lifescience,medical that we oncologists often have difficulty in telling whether our patients are getting better or worse with treatment. Serial radiologic studies are poorly reproducible in lung Selleck 3MA cancer and other tumors that seem to produce “measurable” disease, with discordance rates between radiologists assessing response vs. no response in the range of 15-20% or more (4,8,9). In the case of biliary cancers, the situation is likely worse, with few patients having easily measurable disease. While newer imaging modalities such as MRI or PET scanning may prove

helpful in diagnosis, assessing the response to therapy of a patient with biliary cancer remains a challenge Inhibitors,research,lifescience,medical (1,2,10). In breast cancer and prostate cancer, the serial assessment of CTCs is superior to imaging or PSA determination, respectively, in predicting patient outcome (4,6). The ability to reproducibly and rapidly assess the response to treatment of a patient with biliary cancer would aid drug development by allowing accurate assessment of the effects of novel agents. Inhibitors,research,lifescience,medical Moreover, if “drugable targets” for biliary cancers can be identified, Inhibitors,research,lifescience,medical the ability to serially assess the expression and modulation by therapy of these targets would represent a useful tool for understanding the biology and improving the treatment of these tumors. While the ability to interrogate circulating tumor cells is at present limited, preliminary studies have indicated, for instance, that HER2 expression can be assayed in the CTCs of patients with breast cancer, and can lead to novel insights (11,12). The possibilities

discussed in the paragraph above are intriguing, Inhibitors,research,lifescience,medical but how do we get from here to there? First, the optimal cut-off for the number of circulating tumor cells associated with a poor outcome needs to be established. For breast and prostate cancer, this number has been determined to be more than 5 CTCs per 7.5 mL of blood (5,7). For colorectal cancer, Clinical Microbiology Reviews this number has been determined to be greater than 2 CTCs per 7.5 mL tube of blood (6). Ustwani and colleagues chose the lower number, but this pilot study is not sufficiently robust to determine the optimal cutoff number, and additional studies will need to be done. The observation of a trend for a worse survival in the patients with higher CTC numbers suggest that CTCs may prove to be a useful prognostic marker as it is for breast, lung, and colorectal cancer, but again additional, larger studies are needed to establish this possibility.