In 2013, the Dana-Farber Cancer Institute in Boston applied for a patent on something they called “Dynamic BH3 Profiling.” The patent description summarizes the invention as relating to “methods of predicting response to chemotherapy and in particular targeted therapies.”
This week, in the journal Cell, Dana-Farber researchers published their latest results of testing using this technique, showing that they can predict which chemo treatments will be most effective against a patient’s individual tumor within 16 hours of beginning the test. Such “real-time” testing will help achieve the goal of personalized treatment plans in cancer patients.
The Dana-Farber researchers, headed by Dr. Anthony Letai, has tested a wide variety of solid tumor and blood cancers using Dynamic BH3 Profiling, or DBP, including non-small cell lung cancers, breast cancers, colon cancers, leukemia, lymphoma, and multiple myeloma. To assess the accuracy of DBP, the researchers used the test to predict outcomes in patients taking standard treatments. DBP not only predicted cytotoxicity at a later time, but also predicted progression-free survival. Letai claims the DBP test is 80-90% accurate in predicting the best chemo treatment for an individual tumor sample, among a list of 20 popular common chemo drugs.
DBP measures how close a cancer cell is to apoptosis, or programmed cell death, a common destructive mechanism initiated by chemotherapy drugs. It detects an advance signal that a cancer cell is susceptible to the chemo drug, and this correlates with efficacy down the road. The test is performed on live tumor cells extracted from the patient, or viable cells from frozen tumor tissue. However the test can not work with cells preserved in the commonly used formalin.
Letai explains, “Regardless of the pathway inhibited, or what kind of cell the cancer started in, early drug-induced death signaling predicted later cytotoxicity.” The testing can also help predict the efficacy of combinations of therapeutic drugs. Genetic profiling is also a powerful way to predict drug sensitivity in tumors, but DBP can be done almost in real-time (overnight) and can detect properties in addition to genetic mutations which may point to certain treatments. In the future, DBP may be used in combination with other forms of testing to help create highly personalized treatment regimen.
DBP is still in the experimental phase, and Dana-Farber intends to continue testing the process with more series of patients in clinical trials. They hope to move the test into a clinical setting in the next couple years.