New York Academy of Sciences
New York Academy of Sciences

The results from a unique new pilot program conducted by scientists from the Icahn School of Medicine at Mount Sinai show that multidimensional genomic profiles outperform the targeted cancer panels used currently in many clinical laboratories. The Mt. Sinai team developed and tested the personalized cancer therapy program using an integrated genomic approach that led to therapeutic recommendations for 91% of enlisted patients.

As next-generation sequencing technology has become more affordable, clinical labs have rapidly adopted targeted sequencing panels that scan tumor DNA for variants known to cause cancer. The genetic variants specific to a patient's tumor are important for guiding the choice of cancer treatment. In the current personalized cancer therapy program, researchers generated much more data about the genetic makeup of both patients and their tumors to determine whether this in-depth characterization led to better results.

“There is tremendous interest in tailoring cancer treatment for each patient, since every tumor has its own unique signature of genetic variants that shape progression and response to therapy,” explained co-senior study author Rong Chen, Ph.D., assistant professor of Genetics and Genomic Sciences and director of clinical genome informatics within the Icahn Institute at Mount Sinai. “We launched this program with the idea that a more comprehensive view of that variant signature would make a difference in patient treatment, but even we were surprised by just how much is being missed with current testing.”

The study investigators were able to analyze whole exomes, gene expression, copy number variation, and gene fusions for both tumor samples and matched normal samples for an initial group of 46 patients. Participants had a wide range of cancer types—including colon, thyroid, and breast—and many were in advanced stages of the disease.

In 42 of the 46 cases, the integrated genomic profile led to medically actionable genetic variants with implications about drug response, toxicity, or prognosis. Moreover, the researchers ran commercially available targeted cancer panels for each sample, finding that these tools failed to detect medically actionable variants for many patients. All results were returned to patients and their physicians, and in several cases the information led to changes in treatment.

The findings from this study were published recently in Genome Medicine through an article entitled “Development and clinical application of an integrative genomic approach to personalized cancer therapy.”

“The argument against this integrated approach is the added cost of using multiple analysis platforms. But for patients battling cancer, it's hard to put a price on information that may lead to more successful outcomes,” noted co-senior study author Eric Schadt, Ph.D., professor of genomics at the Icahn School of Medicine at Mount Sinai, and founding director of the Icahn Institute for Genomics and Multiscale Biology. “We believe labs could maximize benefit by implementing a staggered approach, starting with targeted panels and incorporating multiscale characterization for patients lacking medically actionable variants.”

Also of Interest