Leveraging Differences

I was at a cancer research meeting out of town recently, and three men walked into the hotel conference room just before our session was about to start. They picked up donuts and coffee at the back of the room before heading toward some open seats. However, they seemed ill at ease as soon as they looked around the room. Very quickly, they turned around and left (but in their hurry to get out of the room, kept the donuts).

On my way up to my hotel room that evening, I was joined in the elevator by a group of men who were wearing name tags that indicated they were attending a trial lawyers’ convention taking place in the same hotel. At that point, I realized what had happened that morning. The three men must have been looking for the trial lawyers’ conference. After mistakenly walking into our meeting, they realized immediately that those around the room had limited fashion sense, with many, including me, being tie-less and wearing inexpensive blue blazers. This was a clear sign something was amiss, given that the standard attire for the trial lawyers centered more around impeccably tailored suits.

Both meetings continued the next day. Once I knew the signs, I was able to distinguish the trial lawyers from the cancer researchers from across the lobby.

At this point, I must ask forgiveness from my lawyer friends as I compare cancer cells to the trial lawyers who walked into our room.

Cancer cells are similar to normal cells in many ways. Most of the molecules and subcellular parts in cancer cells and normal cells are the same. However, cancer cells often go where they don’t belong, and are nourished by resources that are not intended for them. It can be hard to distinguish the cancer cells from normal cells – unless you know the differences.

We have made great progress over the past two decades in figuring out the differences between cancer cells and normal cells, and can increasingly guide the immune system to recognize these differences (molecules in cells – attire in my story). The next step is to figure out how to use this information to get rid of the cancer cells. The trial lawyers left our meeting as soon as they realized they were in the wrong room. Unfortunately, the same is not true of cancer cells – they do not leave voluntarily

At this time, I would like to point out to my lawyer friends that this is only a metaphor, and I am not really in favor of getting rid of trial lawyers.

Eliminating cancer cells, even if we know how they are different, is a very difficult problem. A key aspect of the immune system that is very finely tuned is its “off” switch. We don’t want our immune system to be fighting our own normal cells. Even if the immune system starts to reject the cancer, the immune response often gets turned off when the system perceives that maybe the cancer “belongs” and should not be removed. To the immune system, maybe that is a cancer researcher in an impeccably tailored suit who is actually in the right room.

This is where very exciting recent research advances become important. We have figured out the nature of the immune system “off” switch (two molecules in this category are called CTLA-4 and PD-1) and now have treatments in the form of monoclonal antibodies that prevent these molecules from turning off the immune system. The result is that a robust anti-cancer immune response can be maintained, in some cases long enough to give the immune system time to reject the cancer. Indeed, a new drug that enhances the ability of the immune system to reject cancer cells was approved by the FDA just last week.

We still have a lot to learn about the best way to use this new class of immune system drugs (together called “checkpoint blockade”) to treat patients. Nevertheless, this is a true breakthrough in our ability to not only distinguish cells who belong from those that do not belong, but to actually maintain the immune response long enough to leverage those differences so they result in elimination of the cancer cells.

One final disclaimer – I really do hope my lawyer friends forgive me for one concluding lawyer joke.

Take that cancer. And you suit-wearing, donut-eating trial lawyers …