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.

Last Warren Village night

My fourth and last Warren Village session was this past Wednesday night. I've enjoyed pediatrics much more than I thought I would. I'm sad, though, because I will not be doing Warren Village next semester. The number slots is very limited, and I know that many of my classmates also want the opportunity to do this elective.

All four of my attending physicians at Warren Village have been fantastic: happy with their jobs, low-key, and eager to educate. They have also been very understanding of the fact that, in terms of medicine, I'm basically starting from scratch.

One of my patients on Wednesday was a teenage boy who complained of severe acne, mostly localized to his forehead but also spreading through his scalp. His mother was a "well-informed medical consumer" and wanted to know about more aggressive treatments for acne. On examination, though, this boy's skin looked exceptionally clear for complaining of severe acne.

When I presented this case to my attending, I made the rookie mistake of neglecting to mention that this boy also likes to use hair gel (a fact that came out while questioning Mom) but that he wasn't wearing any today. So, when the attending physician came in, he started working under the assumption that, like many other kids his age, he was just extremely sensitive to the self-image issues that accompany acne. Once the attending uncovered this hair gel issue, though, he soon concluded that this boy was suffering from dermititis as a reaction to the hair gel.

I felt stupid for forgetting to mention such a relevant piece of information, especially since acne typically doesn't even extend much past the hairline. But, the attending physician turned the mistake into a great learning experience. First, he provided an example of the type of questioning and investigation necessary to move past distractors and mis-information to get to the bottom of a presentation of symptoms. Second, afterward, he owned his own mistake of too quickly buying into the acne story instead of starting the examination tabula rasa.

This is the sort of experience that (I hope) will help me become a better doctor.

Art class in medical school?

Yes, that's right: art class in medical school. And it was part of the required Foundations of Doctoring curriculum, not an elective. Needless to say, I was skeptical that spending three hours of my Tuesday afternoon in art class was a better use of my time than, say, studying for the cellular biology test coming up this Friday. Despite my skepticism (and borderline cynicism), I found this Art in Medicine class useful in helping me learn how to better make observations and report them.

We were given several artworks in small groups. Everyone turned away without looking except for a few people who tried to describe the work of art so that everyone else could visualize it. Then everyone turned around and talked about how their mental image of the painting was different from reality. One difficulty this exercise highlighted was the need for consistent reference points and language to communicate left versus right - which is apparently somewhat of an issue in medicine. Even though sidedness is always described with respect to the patient, people still get confused.

I enjoyed describing the paintings to my classmates, but no matter how thorough and systematic I tried to be, I inevitably left out some detail that greatly changed how my classmates drew their mental image.

Also relevant to the clinic, this exercise highlighted the difference between observation and interpretation. In everyday life, people tend to mix interpretation in with observation. When presenting a patient to an attending physician, though, the practice is to first present hard facts and observations then to use those observations to support an assessment or an interpretation. Take this painting, for example:


What observations can you make about this painting? What interpretations? If you were going to present this painting to an attending physician as you would a patient, what would it sound like? Click here for more information about this painting.