ASCO Update: New frontiers in personalized medicine--the Human Genome

One of the themes of this year's ASCO program reflects the increasing use of biology in making treatment decisions, an idea that just a decade ago was thought to be fantasy--something we would not really see in our lifetime. However, we have already adopted gene testing and molecular profiling in the clinic. The next chapter of sequencing the whole genome of a tumor has just opened with a flurry of publications in the last two years and the formation of diagnostic companies that plan to offer these commercial services--even though most of the sequencing information is not ready to be used in the clinic. At Saturday's breast cancer poster discussion session, there were some early looks at what this future field might look like. One trial in patients receiving the HER2-blocking drug Tykerb (lapatinib) suggested that inherited variants of certain genes involved in HER2 signaling might affect outcome--specifically the cyclin D1 gene, which is involved in cell cycling and can be amplified in breast cancer. Another study refuted earlier findings that acquired mutations (only in the tumor) in the signaling protein PI3 kinase might predict resistance to the experimental HER2-based immunotoxin T-DM1. These early findings need more confirmation in larger trials, but mostly likely, there will be a second generation of markers that tell us specifically which drug will be most effective for which cancer, especially for targeted agents.This point was hit home much more dramatically in today's plenary session for a small subset of lung cancers (about 5 percent of all lung cancers) that harbor an altered gene called ALK and treated with crizotinib, an investigational inhibitor of the kinase encoded by this gene. An astounding 57 percent of patients exhibited a response--much higher that typically seen with any regimen. This is an example of such a strong leap in gene testing and targeted therapy that the discussant who commented on this abstract implied that a randomized trial for this agent might not even be needed. Already, testing for ALK is available in some centers and commercial labs, and very soon, detailed genetic testing on lung cancer will become routine for both approved treatments and for choosing the right clinical trial.