Resistance of cancers to traditional, single-drug chemotherapy has compelled the increasing use of a combination of two or more drugs. Therefore, there is an urgent need to identify and develop novel agents that can modify the effects of existing chemotherapeutic drugs. To address this need, Dr. Wolfram Siede, Associate Professor in the department of Cell Biology and Genetics at the University of North Texas Health Science Center (UNTHSC), has developed a screening process for drugs that have activity against cancer and that act as “chemosensitizers”, enhancing the anti-cancer effects of camptothecin or cisplatin. The screening process is carried out in budding yeast (Saccharomyces cerevisiae) using a state of the art technique called the ‘yeast two-hybrid assay’. Specifically, the screen is designed to detect the activation of crosstalk between checkpoint proteins during cell cycle arrest. Cell cycle arrest is a control process that helps preserve genetic stability; it is a normal response to DNA damage and it is frequently defective in cancer cells. Anti-cancer drugs frequently damage DNA and induce cell cycle arrest; the assay measures checkpoint activation, which is a reliable indicator of drug activity.

“Drugs are still hardly ever designed,” says Dr. Siede, “they are found accidentally during the screening of chemical libraries”. These libraries can each contain several hundred thousand different compounds that may include chemicals, or various derivatives of the same chemical, and natural or synthetic compounds. The size of these libraries necessitated the development of an innovative, high-throughput adaptation of the screening method. Collaboration was initiated, via the office of Technology Transfer and Commercialization at UNTHSC, between Dr. Siede and UHV Technologies Inc. to build the machinery for robotic, high throughput screening of chemical libraries.

Their joint venture was awarded a Phase I Small Business Innovation Research (SBIR) grant. Dr. Siede works closely with engineer Manuel Garcia at UHV. Patents have been filed for the screening assay and the machinery. Other partnerships within UNTHSC have also been established for performing the mammalian experiments to further test and evolve lead compounds identified during the yeast screening process.