2011 brings the 10th anniversary of the first publications of the sequence of the human genome. These reports capped about a decade of efforts to unravel the primary sequence of the DNA in humans that were made possible by the molecular biology revolution. Since that time, we have witnessed the deciphering of the genome of many other organisms, from bacteria to plants. One might wonder how this information can help those who worry about cancer — as patients or as physicians/scientists or as concerned members of the human race. This is an especially timely question, as the technology of DNA sequencing (like computer chips) is advancing at a truly breathtaking pace, raising the possibility that it will be possible to sequence the DNA of an individual cancer or an individual person for about $1,000 in the near future. What has not advanced quite so rapidly is our ability to synthesize this vast amount of information in a cost-effective way, nor is it always easy to use this information to assist the individual cancer patient.
Nonetheless, modern clinical oncology increasingly rests on molecularly-informed decisions. Take the problem of certain types of hereditary cancers. It is now standard practice to offer the possibility of testing for germ line mutations in the BRCA1 and BRCA2 genes to certain individuals who have strong family or personal histories of breast and ovarian cancer. Why test? Healthy individuals who have a germ line mutation of either gene are at high risk for the development of breast and ovarian cancer and may wish to avail themselves of enhanced screening or preventive surgery. Patients whose tumors show these mutations may benefit from a new category of drugs, the PARP inhibitors. In the same way, gene testing strategies also exist for families with a hereditary pattern of colon cancer or some endocrine cancers where knowledge about the presence or absence of a mutation can drive decisions about screening and prophylactic surgery in far more sophisticated ways than would acquisition of a traditional family history alone.
For patients with diagnosed cancers, the value of “personalized” cancer medicine is also emerging at a rapid pace. We have come to recognize that breast cancer or lung cancer is actually an umbrella diagnosis for a variety of molecularly distinct illnesses that arise from the tissue of origin. The presence of genomic changes — changes in the sequence of DNA or the number of copies of a gene within the cell — can help us to estimate prognosis and guide selection of therapy. Consider the value of identifying a mutation in the EGFR gene in non-small cell lung cancer — a signal that the small molecular inhibitor, erlotinib, may be of use — or extra copies of the HER-2 gene in breast cancer — an indication that the agents, trastuzumab or lapatinib, might be active.
Today we tend to use these genetic alterations one at a time to guide clinical decisions. But we are preparing for the multiplex assay, the genetic fingerprinting of each cancer and each host, that is within striking distance. Here at the University of Pittsburgh Cancer Institute (UPCI) and UPMC CancerCenter we will celebrate the 10th birthday of the human genome and our own 25th anniversary with a special symposium on next-generation sequencing on March 10, 2011. Experts from across the US and our own Pittsburgh community will come together to review what we have accomplished. But the real challenge and excitement will come from our discussion and planning for what is to come next in the molecular era. Will the $1,000 genome become a reality? Will this knowledge improve our ability to care for the individual — with or without cancer? Only time will tell. But we at UPCI and UPMC CancerCenter want to be at the forefront of this push into the genetic frontier in the next decade of the 21st century.