Oncologists want to be able to quickly detect cancer drug resistance as many patients experience the tumors shrinking in response to a drug. Having them come back even after successful treatment is something that degrades the quality of life of the patient. Therefore, doctors struggle to find a solution to this problem so that they can identify another drug to which the tumors will respond.
A group of researchers at the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), IBM Research and other organizations have examined a new method for sampling tumors. The new method is an innovation in a traditional process. It is called Liquid Biopsy. In a liquid biopsy, the blood drawn from the patient contains DNA shed from tumors, called circulating DNA or cDNA, which can be isolated or analyzed.
For the research, the team compared the results of both liquid and the standard tissue biopsies from patients who were treated for gastrointestinal cancer but later developed drug resistance. The findings revealed that liquid biopsies provide a deeper insight into both the genetic diversity of the patient’s cancer and the way tumors develop resistance at the molecular level.
“Remarkably, we found that nearly every patient we analyzed had developed not just one, but multiple drug resistance mechanisms simultaneously, and this may be more common than we previously thought,” said Gad Getz, co-senior author of the study, director of the Cancer Genome Computational Analysis Group at the Broad and the Paul C. Zamecnik Chair in Oncology at the MGH Cancer Center. “That is a real paradigm shift and will force us to rethink not just the biology of cancer drug resistance but also how we approach it therapeutically in the future.”
The results explain the reason why cancer, after developing drug resistance, is so hard to defeat. The study also suggests possible molecular mechanisms that underlay drug resistance, which could help new and more personalized therapeutics.
What is the difference between regular biopsies and liquid biopsy?
Tissue biopsies are the first step in cancer diagnosis and treatment, but they are invasive and provide only a glimpse of one location in a single tumor. Liquid biopsies, which incorporate information from multiple tumors, are a promising alternative.
To investigate the efficacy of liquid biopsies, the researchers studied 42 patients with different forms of gastrointestinal cancer who were undergoing treatment with targeted drugs. When the patients showed signs of drug resistance, the researchers analyzed their tumors using both liquid and tissue biopsies. A head-to-head examination of liquid and tissue biopsies showed that in 80% of cases liquid biopsies revealed clinically relevant genetic alterations that are linked to drug resistance.
“This study is the largest to date to directly compare liquid biopsy to tumor biopsy in the setting of cancer resistance,” said Corcoran. “Our findings suggest that liquid biopsy may be the preferred clinical modality for assessing how patients’ tumors have evolved after they’ve become resistant to therapy.”
Liquid Biopsy meets artificial intelligence.
Analysis of DNA from several of the patients in the study didn’t show clear resistance mechanisms. To know more about these cases, the IBM researchers on the team developed machine learning algorithms to group patients together according to shared or similar patterns of genetic alterations linked to drug resistance. By doing this, the researchers were able to suggest possible resistance mechanisms for these cases.
“The IBM, Broad and MGH teams bring complementary expertise and tools to the table while grappling with the difficult problem of extracting meaning from the data, and this interaction has proved to be very fruitful,” said Laxmi Parida, IBM Research Fellow, Computational Genomics, and co-PI, along with Getz, on the Broad/IBM collaboration. “The collaboration has been particularly exciting not only due to the exceptional synergy between the teams but also the invaluable data that are being collected for use by the entire research community.”
Although this new study turned up some interesting findings, the authors explain that larger, more comprehensive efforts are needed to fully understand cancer drug resistance. “To map out the full landscape of cancer resistance mechanisms, we need much larger studies that span a variety of drugs and cancer types,” said Getz.