Jeremy P. Segal, MD, PhD, is the Director of Clinical Development and Policy at NYGC.

DNA sequencing technology has evolved so rapidly over the past few years that, in certain fields, our knowledge and imagination have yet to catch up with the technology. Genetic diagnostics for cancer is one notable example. We have learned so much about cancer at a genetic level, yet translating that knowledge into useful diagnostics has been a frustratingly slow process. There have been many reasons for this, but they can be generally categorized into issues with technology, historical context, regulatory oversight, and clinical capability.

With the advent of next-generation sequencing (NGS) systems, at least it seems that the main technological hurdles—cost and throughput—have been removed. What remains is to address our remaining problems in the most efficient way possible, such that we can leverage this new technology to gain the greatest amount of helpful information about each individual patient’s cancer.

We know now that cancer is really a disease of the genome, originating as a result of multiple mutations of our own genetic code to turn our own cellular machinery against us. Intriguingly, despite the similar histologic appearance of particular tumor types across multiple patients, genomic research is uncovering extreme heterogeneity from tumor to tumor at the level of the DNA. In many ways, each patient’s cancer is a unique disease, albeit with similar features; therefore, we must ultimately turn to genomics-based analysis if we are to develop the most effective personalized approach to each patient’s cancer. The challenge for everyone in the field is how to do this and how to integrate the old with the new.

Of all cancers, those currently most clinically dependent on molecular diagnostics are the hematopoietic (blood lineage) malignancies, while solid tumor diagnostics have lagged behind. For breast cancer patients, we now routinely examine tumor estrogen and progesterone receptor expression and Her2-neu gene amplification to gauge potential responsiveness to Tamoxifen and Herceptin, respectively. Lung cancer has been a particular focus of interest over the past several years. We have recently learned about many of the driver mutations in lung adenocarcinoma and now have a couple of powerful drugs confirmed to be effective when targeted towards mutations in specific genes (i.e. Erlotinib for EGFR-mutated lung adenocarcinoma), as well as clinical trials that aim to target others. The list of target genes goes on, but it doesn’t go on that far.

In the tumor diagnostics laboratory, mutations are typically assayed one at a time, or grouped into small panels, at a cost of hundreds or even thousands of dollars for each particular genetic anomaly. With the incredibly cheap sequence data that can now be produced by next-generation instruments, this boutique analyte-by-analyte testing paradigm seems quaint, and is rapidly becoming obsolete. The question is how to best take advantage of the new technology to provide the most value for our patients.

To that end, the National Cancer Institute (NCI) just recently hosted a meeting titled “Next Generation Sequencing as a Tool for Clinical Decision-making in Cancer Patient Management”  in Bethesda, Maryland. Organized by Barbara Conley and Mickey Williams of the NCI, the meeting was a chance for a group of diagnosticians, researchers, and oncologists, as well as industry representatives and regulatory officials, to meet together and weigh in on the future of cancer diagnostics.

Details on the conference will be published in Part II of this blog post.

About the New York Genome Center

The New York Genome Center (NYGC) is an independent, non-profit organization that leverages the collaborative resources of leading academic medical centers, research universities, and commercial organizations. Its vision is to transform medical research and clinical care in New York and beyond through the creation of what will be one of the largest genomics and bioinformatics facilities in North America.