Mount Sinai researches have finished the first ever clinical trial using RNA-sequencing-based drug repurposing to find effective therapies for multiple myeloma patients (potentially for any cancer). Dr. Samir Parekh and his genomics and precision health colleagues at Mount Sinai created this first-ever trial to better inform the way patient’s therapies are chosen. The trial involved 64 patients who had run out of treatment options and many of whom had been referred to hospice.
The trial sequenced the DNA and RNA of patient’s cancer for cancer-driving mutations. Then Dr. Parekh, and genomics and precision health colleagues, matched the mutations against a database of FDA-approved drugs for therapies that would exploit the mutations to kill cancer. Timing in this trial was crucial as these end-stage, drug-resistant patients could die in days or weeks. So, after finding a backlog on shared institutional supercomputers to be too long to wait for patients who don’t have time, the researchers got their own supercomputer they named Dr. Crusher (based on a Star Trek character).
The drug combinations that Dr. Crusher found extended many patients’ lives and gave them back quality of life, and the researchers have already secured funding to develop a next-generation clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan. Due to the promising findings of this trial, Dr. Parekh and his colleagues are in discussions with major collaborators to enable expanding these studies to all multiple myeloma patients at Mount Sinai soon. However this,s RNA-sequencing and drug-finding platform also have implications in cancers beyond multiple myeloma.
“Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients,” said researcher Samir Parekh, MD, Associate Professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences and Director of Translational Research in Myeloma at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. “The trial has allowed us to test the accuracy of our platform, laying the foundation for our next-generation precision medicine framework.”
The results of this study showed that a comprehensive approach that includes RNA sequencing can provide more treatments for patients with advanced disease beyond the standard DNA analysis currently available. A majority of the patients in the trial received a drug based on their cancer’s RNA profile and many benefited from their personalized treatment plans.
“Current approaches in precision oncology aim at matching specific DNA mutations to drugs, but incorporation of genome-wide RNA profiles had not been clinically assessed before now,” said researcher Alessandro Lagana, PhD, Assistant Professor of Genetics and Genomic Sciences at the Institute for Next Generation Healthcare and the Icahn Institute for Genomics and Multiscale Biology at the Icahn School of Medicine at Mount Sinai. “We expect RNA sequencing will play a larger role in the precise delivery of targeted drugs in oncology.”
Mount Sinai researchers have already received funding to develop a next-generation clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan.
“This research is part of an accelerating paradigm shift in cancer therapy, where treatment may be given based on the specific genomic alterations observed in a patient’s tumor, rather than on the tumor histology or tissue type,” said Joel Dudley, PhD, Executive Vice President for Precision Health, Director of the Institute for Next Generation Healthcare, and Associate Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. “RNA sequencing will likely complement current precision medicine strategies in the near future due to its ability to capture more dynamic aspects of unique tumor biology and provide information beyond what is capable with DNA alone.”