Screening for anti-cancer drugs

A test that predicts an individual cancer patient's response to different drugs is about to enter clinical trials, developers have announced. The chances of successful treatment will increase, they predict, while costs will decrease.  

The test is based on an electrochemical device developed by Oncoprobe, a spin-out company from the University of Manchester, UK. The device will detect the chemo-sensitivity of an individual patient's tumour to a range of anticancer drugs.  

With less than a 50 per cent success rate, dropping to around 20 per cent with some drugs, chemotherapy efficacy depends on a patient's genetic make-up, metabolism and any specific resistance of their cancer type. Many patients are therefore exposed to unnecessarily debilitating drug toxicity, and dangerous delays in effective treatment, which worsens their condition. 

The new device measures cell membrane electric potential. All cells generate a membrane potential thanks to their internal enzyme redox chemistry. Oncoprobe's ultra-sensitive electrochemical assay consists of a biosensor that detects and measures real-time in vitro changes to this cell membrane potential, thus indicating the effects of anticancer drugs on tumour cells.  

The technology evolved out of personal tragedy. University of Manchester scientist David Geary's wife died of cancer. Friend and colleague biochemist David Woolley told Geary that clinicians could not predict patient response to chemotherapy. As a corrosion scientist, Geary wondered whether electrochemistry could be used to predict which drugs would knock out cancer cells. Oncoprobe spun out from the University of Manchester in 1999 after a third scientist, Bob Eden, developed a working prototype.  

Oncoprobe developed a disposable bioassay unit in collaboration with Derbyshire-based instrument makers Uniscan Instruments. It comprises eight culture wells each containing three gold sensors positioned around a reference electrode. This arrangement allows simultaneous testing of a patient's biopsied tumour cells to determine how different drugs or drug combinations affect them.  

Oncoprobe scientists had previously shown that tumour cells attach to a gold electrode and produce an electrochemical open circuit potential (OCP) that undergoes reproducible changes when responding to anticancer drugs. This produces detectable changes in cell-membrane potential well before other morphological changes.  

The bioassay unit's success is due to the passiveness of the technique. 'We don't do anything to the cells,' said Oncoprobe chairman, Jim Bristow, 'simply take them as a biopsy, separate them from normal cells, and put them into the sensor to be measured.'  

After successful results on laboratory rats, Oncoprobe are about to start human trials.  

Lionel Milgrom