Picking The Lock…

Most everyone has heard the old adage that the three most important things in real estate are "location, location, location".  If you were to use a similar approach for cancer therapeutics it might be "specificity, specificity, specificity".  To my mind, 'specificity' may be the single most important attribute for any cancer therapeutic to be maximally effective, and therefore the search for absolute specificity is in many ways the Holy Grail of cancer research.

Why do I say this?  To start with, there is a myth in the public's mind that it is difficult to kill cancer cells.  Frankly, this is nonsense.  Generally speaking, it is very easy to kill cancer cells.  What is difficult is killing ONLY cancer cells and leaving normal cells unscathed. This is where, by and large, cancer treatments of the past have failed us. 

But aren’t anti-cancer drugs, by their very name and nature anti-“cancer” drugs? There is where a second misconception enters the fray: that most chemotherapeutic agents have been specific anticancer drugs.  Actually, for the most part, most of the “classical" chemotherapy agents have in fact been drugs that interfere with cell division as opposed to being anticancer drugs per se. In fact, most of these drugs of the last generation target rapidly dividing cells, not necessarily only cancer cells. 

While it is very true that most cancers are comprised of rapidly growing cells, unfortunately they are not the only cells in the body that divide rapidly. For example, for those unlike myself were not follicularly challenged <smile>, your hair cells divide rapidly and replenish quickly. The cells in your digestive system and your gut are being replaced at a very fast pace.  And the cells that populate your blood system are also dividing quickly and on a constant basis to provide a (usually) never-ending supply of blood cells of all sorts.

By now, you can probably see where I'm going with this.  What are the major side effects at we usually associate with chemotherapy?  Your hair falls out, you get sick to your stomach, and more often than not you get anemic.  That's because the normally rapidly-dividing cells in your hair, your gut and your bloodstream are also under attack. The chemotherapeutic agents interfere with their rapid division in much the same ways they interfere with the rapid cell division of cancer cells.

So the trick is to discover and develop treatments that recognize truly unique properties of cancer cells, i.e., properties that are not shared with non-cancer cells. Simply targeting rapidly dividing cells is no longer be adequate (not that it ever was...).  We need to discover better signposts that define and identify cancer cells as opposed to normal cells.  We need to find new ways to make cancer cells stand out from the crowd, ways that make cancer cells scream out at us "I am the cancer cell.  Don't waste your time with those other normal cells. Take me!"
 
Look at the two accompanying pictures: I like to think of this as the old barn door analogy.  No longer is it acceptable to do a scatter-shot at the side of the barn in the hopes of hitting the barn door.  Now we want to go in and pick the lock...

I doubt that very many of my cancer research colleagues would appreciate being called the next generation of lock-pickers, but in one very real sense that's exactly what they are! The more and more specific, the more and more targeted and the more and more selective we can make our future cancer therapeutics, the better will be the treatment, the better will be the outcome for patients and the better will be the quality of life for patients during and after treatment.

This notion of targeting and specificity will be a constant thread throughout many of the posts to follow. You've all heard by now, I am sure, of the notion of "personalized medicine" or a related term "precision medicine".  This is a very important part of the whole notion of attaining maximum specificity in the treatment of cancers of all types.