Advances in Genomics Mask Complexities

Neil L. Spector, MD

Co-director, Experimental Therapeutics Duke Cancer Institute Duke University Medical Center Durham, North Carolina

Technological advances in genomics have prompted a “sea change” in breast cancer drug development and treatment, but much more work must be done to understand the full implications of gene mutations so that therapies can be truly targeted to individual patients.

That was the picture Neil Spector, MD, painted as the 29th Annual Miami Breast Cancer Conference got under way in Florida on Wednesday. Spector is the co-director of Experimental Therapeutics at Duke Cancer Institute, Duke University Medical Center in Durham, North Carolina.

“The influence of genomics on drug development is not as simple as it sounds and not as straightforward,” said Spector.

Genomic advances have led to the identification of “high-value targets” for drug development, he said, with breast cancer leading the way in defining molecular subtypes. In addition, genomics has helped shorten the timeline from the discovery and validation of a target to an FDA-approved therapeutic.

Indeed, Spector said it is possible that within the next five years patients with breast cancer will be able to walk into their oncology specialist’s office with a full genomic sequencing of their tumor on a computer flash drive at a cost of $100 or less.

At the same time, however, Spector said the impact of such extensive genomic knowledge on treatment outcomes has not been established. “We’re generating lots of data but we don’t know that all that data is necessarily meaningful,” he said in an interview.

Recent research has demonstrated the molecular heterogeneity of tissue samples even within the same biopsy (N Engl J Med. 2012;366:883-892), Spector said. Moreover, he said, the “omics” of the cancer cell alone will not tell the full story of the disease.

It is important to determine how gene mutations in cancer cells fit into complex, interrelated cell-signaling networks, Spector said. The tumor microenvironment, including such factors as inflammation and stress the patient might be facing, should be taken into consideration, he said.

He cited the “seed and soil” hypothesis of metastasis, first proposed in the 1880s, to express the importance of factors that support a cancerous cell. “Cancer is a systems disease,” he said. “It’s not one cell, it’s a diseased cell sitting in an environment that’s allowing it to grow.”

However, technological advances in genomics might raise hopes for breakthrough treatments to unrealistic levels, Spector said.

“The expectations that the era of genomics is going to solve all the problems by getting a biopsy [from a patient], sequencing that biopsy, and that’s all you’re going to need to know—that expectation is going to set a lot people up for disappointment,” he said.

<<< View the On-site Coverage From the 29th Annual Miami Breast Cancer Conference.