INDIANAPOLIS – Cancer patients with advanced disease fared better when they received genomic-guided therapy, according to a study by Indiana University School of Medicine researchers.

Lead and senior authors Milan Radovich, Ph.D., assistant professor of surgery, Patrick Kiel, Pharm.D., adjunct assistant professor of medicine, and Bryan Schneider, M.D., associate professor of medicine and the Vera Bradley Investigator in Oncology, and colleagues found that patients with metastatic cancer (cancer that had spread) that had not responded to other treatments had improved outcomes when they received therapy guided by genomics compared to those who did not.

The study was published online July 15 in Oncotarget.

The researchers found that 43.2 percent of those patients who received genomic-guided therapy had improved duration of response when compared to their own prior therapy compared to only 5.3 percent of those who did not receive such treatment.

"We found patients who had genomic sequencing had better outcomes," Dr. Schneider, also a researcher at the Indiana University Melvin and Bren Simon Cancer Center, said. "What we already know across cancer types is that for each subsequent line of therapy, a patient can expect a shorter amount of time to experience benefit from the therapy. We looked at the percentage of patients who actually beat their prior line of therapy in terms of success. This allowed us to really use each patient as his or her own benchmark."

Dr. Schneider added: "While there has been incredible enthusiasm for use of genomics to help guide patients to personalized therapy, there still needs to be additional evidence that this approach helps patients.

"This study gives us evidence in a real clinical world with patients with a variety of tumors who are getting a variety of therapies – both on and off clinical protocol – that they do indeed gain a benefit."

The research team studied 101 patients from the Indiana University Health precision genomics program with metastatic solid tumors who had progressed on at least one line of therapy. The patients' tumor samples were submitted for DNA and RNA next-generation sequencing. The majority of patients had a diagnosis of soft tissue sarcoma, breast cancer, pancreatic cancer, or colorectal cancer, although multiple others were included.

"An important aspect of our program is the deliberation of genomic results by a multi-disciplinary advisory board composed of more than 20 IU faculty and IU Health staff encompassing medical oncologists, genomic scientists, pharmacists, pathologists, nursing, and bioethicists," Dr. Radovich, also a researcher at the IU Simon Cancer Center, said. "As the landscape of precision medicine evolves, both technologically and clinically, having access to broad-based academic expertise will be critical to ensure that every facet of potential treatment avenues is explored."

Dr. Schneider said genomic-guided therapy can help patients by matching the acquired genetic mistake seen in the tumor with a drug that is designed to target that genetic vulnerability.

"Each of us carries an amazing blueprint in our DNA, which is our genome," Dr. Schneider said. "The genome is made up of about three billion letters. Think of it as an instruction manual or blueprint. We can get mistakes or changes in that blueprint that can make it difficult for the cell to read the instruction manual. When that happens, the cell misbehaves and becomes cancerous.

"The goal behind using the genome in cancer therapy is not to only understand why these mistakes might make the cancer occur but also to learn that these mistakes might lead to an understanding of the tumor's vulnerability. For those vulnerabilities where we have drugs either in trials or already approved that are known to attack the vulnerability, we can match that vulnerability with that drug."

Because of the emerging body of evidence that shows better outcomes with genomic-guided therapy, the authors wrote that it should be considered with appropriate patients to help guide patients to clinical trials or optimal therapies.

Other authors from Indiana University included Bert O'Neil, Safi Shahda, Paul Helft, Todd Skaar, J. Thomas Callaghan, Nasser Hanna, Roberto Pili, Patrick Loehrer, Daniel Rushing, Darrell Davidson, Mehdi Nassiri, Liang Cheng, Lawrence Einhorn, Natraj Ammakkanavan, and Guanglong Jiang, and Meagan Ferguson, Megan Parsley, Erin Niland, and Stacy Nance of the IU Health precision genomics program.

The study was made possible in part by a grant from the Walther Cancer Foundation.

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