Matching cancers and chemical treatments

Matching cancers and chemical treatments

Matching cancers and chemical treatments
When oncologists meet a new patient affected by a cancer, they have to take decisions about the best possible treatment. Now, U.S. researchers have devised an algorithm which matches tumor profiles to best treatments. They've used a panel of 60 diverse human cancer cell lines from the National Cancer Institute -- called NCI-60 -- to develop their "coexpression extrapolation (COXEN) system." As said one researcher, "we believe we have found an effective way to personalize cancer therapy." Preliminary results have been encouraging and clinical trials are now planned. But read more...
This research work has been led by Dan Theodorescu, a University of Virginia oncologist and cancer biologist, with the members of his lab and Jae Lee, a computational biologist and bioinformatics statistician.
So how did they start their research effort? "Using a panel of 60 diverse, human cancer cell lines from the National Cancer Institute (NCI-60), the researchers devised and tested an algorithm designed to match the best potential treatment(s) for a particular tumor in a particular patient. Previously, the NCI-60 cell lines were used to screen more than 100,000 chemical compounds for their anticancer activity. These drug responses, however, were not definitely linked to clinical effectiveness in patients. Another issue is that the 60 cell lines did not include all important cancer types (for example, certain bladder cancers, lymphomas, and small cell lung cancers were not among the 60 lines studied)." For more information about NCI-60, here is a link to a list of the 60 human cancer cell lines used in the in vitro screen.
The researchers say that their COXEN system also can be used for data mining purposes, such as identifying chemical compounds to treat a specific cancer. "The most exciting aspect of this research is that in addition to predicting patient responses to therapy, the COXEN algorithm can be used to discover effective compounds in any form of cancer. By the nature of the algorithm, which examines both cancer cells and drug activity at the molecular level, these newly discovered drugs should be effective in patients. This pre-screening for effectiveness using COXEN should greatly lower the failure rate of clinical trials testing new compounds. Likewise, as the drug discovery times are decreased in research laboratories, the cost of drugs also will come down."
The University of Virginia news release was probably published too early. First, it says that the research work about this algorithm has been published on July 23, 2007 in the Early Edition of the Proceedings of the National Academy of Sciences. It's not online yet, but check by the end of the week. Second, it announces a web-based COXEN system (www.coxen.org) "where investigators with genomic profiling data from cancer cells or patient tumors can obtain chemosensitivity prediction results on FDA-approved chemotherapeutic compounds." The website doesn't exist yet, and a page found in the Google cache states that the site will open in September 2007.
Luckily, the University of Virginia Patent Foundation provides more information about COXEN, an "In Silico Prediction of Chemotherapeutic Response," saying it's a "methodology to predict the efficacy of a chemotherapeutic agent. The technique can be utilized for drug discovery or in diagnostic applications."
And here is a description of how COXEN was used. "To demonstrate the power of the COXEN methodology in drug discovery applications specific sensitivity markers were identified for a large set of drugs to a panel of 60 cell lines (the NCI-60 public data set). There are no bladder tumors on that data set. By comparing bladder carcinoma expression profiles, and drug sensitivity profiles, a drug candidate with high potency against bladder carcinoma cells was identified. Through the elimination of irrelevant clustering between the NCI-60 cell lines the identification of the different drugs sensitivity profile was enabled. For one drug, this profile was highly prevalent in bladder cancer cell lines. Initial in vitro data indicates that this particular compound has a better response rate on bladder cancer cells than any other drug currently in use, including Cisplatin."
So what's next? "Dr. Theodorescu is planning clinical trials for the new compounds against bladder cancer. Another planned clinical trial would examine patients with a variety of cancers receiving COXEN personalized, second-line drug combinations to beat their cancers, using FDA-approved agents. Many new and exciting discoveries remain to be made, even more quickly and at lower costs."
Now, let's see what will happen in the next months -- or years. But it's definitively an interesting approach.
Sources: University of Virginia News, July 23, 2007; and various websites
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