Genomics-based medicine improving patient lives

Cell-killing chemotherapy drugs, the mainstay of cancer treatment, are among the most toxic instruments in the clinician’s toolbox. These drugs are associated with a myriad of side effects, ranging from hair loss and infections to neurotoxicity or even induction of new cancers. Thus, doctors and patients alike welcomed the news from the TAILORx clinical trial published earlier this summer in The New England Journal of Medicine showing no benefit to the inclusion of chemotherapy treatment alongside hormone therapy for the majority of women with the most common form of breast cancer. These results suggest that tens of thousands of individuals diagnosed with breast cancer annually may be able to avoid chemotherapy without compromising their health. However, behind this headline-grabbing discovery lies another victory, one that enabled this shift in the way we treat cancer.

Since the beginning of the Human Genome Project in the 1980s, the study of DNA, the genetic code embedded in all cells, has promised to provide a more precise understanding of human diseases and the ways they should be treated. In recent years, some have grown skeptical of the utility of genomics in routine clinical practice. However, studies such as the recent TAILORx clinical trial demonstrate that genomic-based medicine is truly improving the lives of patients. Indeed, in scientific labs, a new, intricate understanding of cancer will continue to build upon the early successes of genomic medicine.

This growing scientific body of knowledge raises the question: What will the TAILORx trials of the future look like?

The most straightforward upgrade will come from looking at a broader set of genes; the TAILORx trial looks at a mere handful of genes, and more recent efforts have implicated several hundred genes in cancer. Moreover, by analyzing tumor samples from patients newly diagnosed with breast cancer, clinicians in the TAILORx trial used the levels of expression of genes to determine which were the most activated. In addition to assessing gene expression, future studies must also integrate information regarding mutations in genes involved in cancer. And, while much of the focus of clinical cancer genomics has been on mutations in genes, vast stretches of DNA in between genes can also be mutated in cancer. These discoveries represent promising avenues that should be comprehensively integrated into clinical cancer research to assess risk and therapeutic response.

Even by profiling the mutations and gene expression of a tumor, a modern view of cancer tells us that we are still missing critical nuances hidden within a patient’s cancer. Recent groundbreaking work has focused on the genetic profiles of individual cancer cells and has dismantled the assumption that all cells of an individual patient’s tumor are identical. In fact, a population of cells representing less than 1 percent of the total tumor might contain a mutation that allows the cells to escape treatment and eventually grow out as a treatment-resistant recurrence of the cancer. Thus, this blossoming technology that allows for the genetic profiling of individual cells may one day be a standard in clinical cancer medicine.

To be sure, not all of these genomic technologies are ready for use in the clinic. Extensive computational work is needed to understand the mountains of data that such tests would generate to effectively separate signal from noise. Indeed, we should be cautious of current genomic sequencing tests available to patients that may oversell the clinical benefit. Additionally, barriers between institutions that limit the vital, large-scale aggregation of deidentified clinical and genomic data will need to be modified, with careful attention to preserving the privacy and antidiscrimination rights of individuals.

Finally, like any new technology, the cost of sequencing technologies is another hurdle that must continue to be addressed. Just as the cost to sequence DNA from a whole genome has fallen drastically from $100 million in 2001 to about $1,000 today, DNA sequencing costs must drop further to allow genomics to take its place alongside blood smears and biopsies as commonplace diagnostic tools in cancer.

It is crucial that stakeholders in the private sector, public sector and academia recognize the power of cancer genomics and work to address the scientific, institutional and cost hurdles that remain. By embracing this critical arena of scientific research, cancer genomics has the power reshape the diagnosis and treatment of cancer and other diseases, giving new hope to millions of patients.

Seth H. Cassel (; Twitter: @seth_cassel) is an MD-PhD candidate at Harvard Medical School and MIT, conducting his PhD research in cancer biology. Cigall Kadoch is an assistant professor at the Dana-Farber Cancer Institute and Harvard Medical School, as well as an Institute Member at the Broad Institute.

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