A new study of a large clinical trial, FOCUS, in patients with advanced colorectal cancer showed that patients with low expression of topoisomerase I (Topo I) did not benefit from irinotecan therapy (a Topo I inhibitor), while patients with intermediate to high expression of Topo I did show benefit from irinotecan therapy. This is an important finding for several reasons. First, although it may seem obvious that expression of the molecular target of a drug would be necessary for that drug to have an effect, this does not always seem to be the case. Although patients need to have HER2 overexpression in order to benefit from HER2 targeted therapies such as Herceptin and Tykerb, high expression of the HER2 family member EGFR has so far not shown a correlation between high expression of the protein and response to EGFR targeted therapy.
Second, topo I inhibitors have long been considered as chemotherapies which are generally given to cancer patients in a one size fits all approach. This new finding may indicate that our older chemotherapies, often seen as hatchets rather than scalpels, may in fact be more selective than previously thought. Although chemotherapies often cause toxicity in many patients, toxicity risks may be more worthwhile if a patient can be identified prior to therapy that is more likely to benefit, thus sparing patients who are not likely to benefit and helping them to find other therapies that they may have a better chance of benefiting from.
At TMD, we have a number of biomarker assays that could be used to assess the impact of chemotherapeutic drugs on relevant cancer associated pathways. We have a great deal of expertise in developing immunohistochemistry assays, such as the one used for the detection of Topo I in this study. We currently have a validated immunohistochemistry assay for the detection of Topo II. If you’re interested in developing an assay for the detection of Topo I, please contact us.