Novel Cell Profiling Technique May Help Personalize Cancer Treatments
Researchers have developed a lab test called Dynamic BH3 Profiling (DBP) to measure early changes in net proapoptotic signaling at the mitochondrion induced by chemotherapeutic agents in cancer cells. In cell-line and clinical experiments, the test accurately predicted chemotherapy response across many cancer types and agents, including combinations of chemotherapy. If validated in ongoing clinical trials, the test could be a method for quickly determining the best treatment for individual patients. The study by Montero et al is published in Cell.
Study Methodology
The researchers exposed cancer cells to short incubations with chemotherapy agents to measure whether the drug exposure induced an increase in priming compared with an untreated control. In this study, the researchers performed DBP on living tumor cells that were removed during surgery or a biopsy or were frozen in a way that leaves the cells viable. The test does not work on tumor samples that have been preserved in formalin, according to the researchers.
DBP was performed on cell lines of many different cancers, including non–small cell lung cancer, breast cancer, colon cancer, ovarian cancer, leukemia, lymphoma, and multiple myeloma.
Study Findings
The researchers found that DBP consistently predicted the most effective therapy among many drugs tested against specific cancer types. In most cases, reported the researchers, the test provided accurate answers within 16 hours after the chemotherapeutics were mixed with the tumor cells.
In an experiment using ovarian cancer cells removed from 16 patients, DBP testing was used to predict which tumors would respond to carboplatin. After 16 hours, the researchers detected robust priming (> 20%) in six of the patient specimens. All analyzed patients were then treated with carboplatin in combination with paclitaxel in the clinic. The researchers found that patients whose cells exhibited a robust priming (> 20%) experienced significantly longer progression-free survival than those patients who did not (< 20%).
“Our results support the model that initiation of death signaling is the main regulator of eventual commitment to cell death. Moreover, we show that we can perform these measurements on primary patient cancer cells in a way that predicts clinical response to therapy,” wrote the study authors.
The Next Step
In the future, the investigators plan to test DBP on tumor cell samples from patients entering clinical trials and compare their outcomes with the test results. If validated in these ongoing clinical studies, the test could be ready for clinical use in 2 years.
Anthony Letai, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author of this study.
Funding for the study was provided by the National Institutes of Health and Beatriu de Pinós programme from la Generalitat de Catalunya in Spain. The researchers reported no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
