TITLE
An Adduct-specific Anti-thymidylate Synthase Antibody for Monitoring Fluorouracil Anticancer Therapy
CASE NUMBER
C11954
ABSTRACT
We developed a functional assay for a class of widely used anti-cancer drugs, 5-fluorouracil and related compounds (SFU). It is well established that SFU works largely by inhibiting the enzyme thymidylate synthase (TS) in cancer cells. Thymidylate synthase, in turn, is essential for DNA synthesis, as it is the critical enzyme for synthesizing thymidine, one of the four bases in DNA. We developed an antibody to measure the degree to which TS is inhibited in tissue biopsies by SFU and related drugs. Assays for TS inhibition are useful 1) to monitor 5FU effects and drug resistance in animal testing or in patients receiving anticancer treatments; 2) to identify compounds having anticancer effects similar or superior to 5FU; 3) to identify compounds that can enhance SFU anticancer activities; and 4) to distinguish whether a cancer is truly resistant to 5FU or instead has not received adequate exposure to the drug. The major novel aspect of this assay and utility is that this antibody uniquely permits an assay that could detect in real-time (fast and easy) the efficacy of 5FU in patients.
FEATURES
An antibody specifically recognizing the inhibited, drug-bound (drug-adducted), form of thymidylate synthase has not been reported. A rapid method to determine whether someone has received an effective dose of chemotherapy has never been introduced into routine cancer treatment practices. On occasion, the concentration of a dosed chemical has been measured in patient blood, but its effectiveness perhaps has not been measured before in patients. In an earlier discovery, we introduced an immunoblot method to measure FU effectiveness in cell culture and in animal experiments, but our previous discovery carried the inconvenience and laboriousness of the immunoblot method. Our newest antibody offers a potential way to bypass the need for a gel separation and membrane, in theory permitting a high-throughput and rapid inununoassay using ELISA or exclusively liquid phase methods.
STAGE OF DEVELOPMENT
Antibody to measure TS inhibition in tissue biopsies
ASSOCIATED PUBLICATIONS
J Clin Oncol. 2015 Mar 1; 33(7): e36–e37.
