Precision Medicine Is More Than Genomic Sequencing

Robert H. Carlson, MBA

Disclosures

October 24, 2016

Back to Pathology

"We can't abandon pathology for the understanding of where the tumor came from; in the end, precision medicine will surely be a synthesis of the old and the new," Dr Huntsman said in his ESMO lecture. "It is important to know what the mutations and genetic alterations are, but it's also important to know what the cell of origin is and the biological context for those mutations, because you can imagine them having different effects in different tissues."

In the end, precision medicine will surely be a synthesis of the old and the new

In 2015, Dr Huntsman and colleagues published their assessment of how cellular context should be incorporated into precision medicine.[2] In an interview, he offered some key points.

"Researchers must understand what portion of the tumor cell has the mutation they want to target—that is, whether the mutation is truncal and found in the development of the cancer, or present in some minor subclone," he said. "If the latter is true, it is unlikely this will be a useful target in that cancer, and you'll probably have to target several mutations at the same time to be successful."

Then there is the question of whether resistance mutations are already in the tumor. "We are discovering that in colon cancer, where a KRAS mutant clone emerges after treatment with anti-epidermal growth factor receptor therapy, those mutations were usually present in the cancer already," Dr Huntsman said.

Another question is whether the mutation is actually active in the tumor at the time of treatment.

"If you're looking at trastuzumab therapy, it doesn't really matter whether the signaling pathway is active because probably what you are doing is stimulating the immune system," he said. "However, for a small-molecule inhibitor of a pathway, if the pathway is inactive, then you're not going to do anything. This is something we as a community are not looking at yet."

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