What is personalized medicine?

A consistent theme that has been hammered into our heads throughout this Molecules to Medicine block is how personalized medicine is the future of medicine. By and large, the current approach to medicine is "one size fits all," which the professors always utter with a negative voice inflection so we medical students are sure to know that this is a bad thing. Personalized medicine, in contrast uses genetic or molecular analysis in order to predict who might respond well to a given therapy over another.

The most well known example of such personalized is in breast cancer. A quarter of all breast cancers are characterized as being caused by a mutation in HER2, human epidermal growth factor receptor (EGFR), which becomes overactive when it's mutated. This EGFR, as its name implies, normally activates signaling cascades that control cell adhesion, migration, and proliferation, cellular processes that are all important in the generation of a tumor. A HER2 mutation thus causes a particularly nasty type of breast cancer, but a drug called Herceptin has been developed that calms down the overactive EGFR by binding to and inactivating it. As you might expect, only patients who are positive for this HER2 mutation will benefit from Herceptin treatment.

Several weeks ago, we learned about Li-Fraumeni syndrome, which is a disease of increased susceptibility to developing cancer at an early age caused by mutation of a particular protein called p53 that is responsible for "proofreading" the genome as each cell is being replicated and fixing any mistakes. If this genome housekeeper gene is mutated, it's all of a sudden much easier to accumulate more and more mutations until, by chance, you get a cell that divides like crazy (in complete disregard of environmental signaling) and acquires other characteristics of a cancerous cell. So, radiation treatment is probably not such a good idea for patients who have a mutation in p53, because the radiation will likely just cause more mutation events that their dysfunctional housekeeping protein p53 is unable to fix.

During this morning's lung cancer clinical vignette, the lecturer again drove home the idea of personalized medicine by showing how one type of lung cancer is responsive to drug A while another type of lung cancer is unresponsive to drug A but more responsive to drug B. A molecular characterization of the exact kind of lung cancer starts to look like a necessary first step before deciding on any therapeutic intervention.

Indeed, for some diseases such as lung cancer, or when a patient's family history is highly suggestive of a mutation in one of those genome housekeeping genes, the standard of care is already trending toward a personalized approach to devising a treatment plan.