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Precision medicine is more than genomic sequencing

Monday, October 24, 2016

This is an excerpt of a story that appeared in Medscape. Read the full feature here

Basing decisions about cancer treatment on mutations and other somatic genomic abnormalities has become a standard of care for patients with some tumors types, but the use of targeted therapies rarely leads to cure, and responses can be incomplete. If clinical decisions are to improve, both mutation data and cell context—the cellular and genomic milieu in which the mutations are found—must be considered.

"Cell context and mutation are the 'evil twins' of cancer," said David G. Huntsman, MD, professor in the Departments of Pathology, Laboratory Medicine, and Obstetrics and Gynecology, University of British Columbia, in a presentation at the recent European Society for Medical Oncology (ESMO) annual meeting in Copenhagen. "Mutation and cell context are the two dominant factors that collude in the development of cancer and shape what a cancer is and how it potentially can be treated."

"We've been focused a little too much on the mutation side of things the past few years because of the excitement around next-generation sequencing, but now we have to rebalance the discussion and consider the cell context as well," Dr Huntsman said, in his lecture titled "One Mutation, Many Cancers."

Understanding how cell context and mutation interplay from the point of tumor origin through development and progression will help predict why some cancers respond to treatment, whereas others have primary resistance to specific therapies, he said. "Once we know that, we'll be able to improve the performance of a lot things we're doing in the clinic."

A good example is the ubiquitous BRAF gene and the prototypical BRAF V600E mutation found in some cancers, Huntsman said, in an interview after the meeting.

"You can't treat all tumors with the common BRAF mutation as being equivalent—targeting that mutation is highly effective in some tumor types and totally useless in others," he said. "Melanomas with the BRAF V600E mutation respond well to treatment with vemurafenib, whereas colorectal carcinomas with the identical mutation do not."

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Dr Mark RubinDr Mark Rubin Mark A. Rubin, M.D., a professor of Pathology and Laboratory Medicine and founding director of the Englander Institute for Precision Medicine at Weill Cornell Medicine, agrees that there has been an overemphasis on the genomic component of precision medicine.

"Precision medicine is not just sequencing; it's looking at a patient in the context of their environment, the type of clinical care they're getting, their interaction with their environment, and then the genomic analyses," Rubin said. "The emphasis has to be on a more holistic view of the individual in the context of precision medicine, looking at the tumor genomics, the patient's clinical information, and their environment."

Tumor cells are in a microenvironment of the patient, Dr Rubin said, and that will be reflected in how the patient responds. Immunotherapy is the best example of this, he said, in that tumor cells can affect the surrounding cells so that they don't recognize the tumor cells.

"That's something typical genomics is not capturing, and it's something new tests need to focus on," Dr Rubin said. "When performing genomic sequencing of the tumor, you should look in parallel at surrounding cells and evaluate the cells in the same types of assays, and only then ask which patients' microenvironments are most likely to respond to a checkpoint inhibitor immunotherapy."