Novel tool to help personalise cancer treatments
The discovery means treatment on patient samples could be tested directly and used to guide therapy
By measuring how vigorously tumour cells turn on ‘self-destruct’ signals when exposed to different cancer drugs, a novel lab test can predict within 24 hrs which agent is most likely to work against a particular tumour, say researchers from Dana-Farber Cancer Institute.
The scientists say this technique could lead to more reliable and rapid tools for ‘personalising’ cancer treatments. Clinical testing has already begun.The team led by Dana-Farber oncologist Anthony Letai, reported in the 26 February online edition of the journal Cell that the test consistently predicted the ‘winner’ among many drugs tested against a wide variety of cancer cells in the lab. In most cases, the answer emerged after only 16 hrs after mixing compounds with tumour cells.
‘We demonstrated that [the test] can be exploited to select among many therapies the one that it is best for a single tumour,’ the researchers wrote. ‘We also demonstrated that it can select among many patients those that are most likely to respond to a single therapy.’
The technique, called Dynamic BH3 Profiling or DBP, is designed to detect the earliest signs that a cancer cell treated with a drug is beginning to destroy itself through apoptosis, a natural quality-control process that rids the body of unneeded or dangerous abnormal cells.
Cancer cells can survive by blocking the ‘pro-death’ molecular signals that trigger apoptosis. Most chemotherapy treatments work by inducing a wave of pro-death signals in cancer cells to overcome the survival signals. The death process may take several days, but with the DBP test, scientists can identify which drug or drug combination has most effectively jump-started pro-death signalling.‘This new technique represents a completely novel approach to precision medicine because we can test possible treatment directly on patient samples to guide cancer therapy,’ said Joan Montero, first author on the report, a postdoctoral researcher in the Letai group.
The test must be performed on living tumour cells removed during surgery or a biopsy, or frozen in a manner that leaves the cells viable. It will not work on tumour samples preserved in formalin, the investigators said.
The Dana-Farber investigators plan to test the predictive power of the DBP technique on samples from patients entering clinical trials and monitor if their outcomes correlate with the test results. Once this initial testing is done, they expect to be using DBP in the clinic in the next couple of years.