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.

Slash and Burn and Poison????

In my travels across the country over the past 20 years or so, one of the most common questions I got was "where's the progress?"  Or "are we really making any progress?".  After all, people often said to me "it's 50 years later and were still slashing and burning and poisoning", meaning that we are still using surgery, radiation and chemotherapy as the basic modalities of our therapeutic armamentarium.

Since I am not a physician, and therefore do not treat patients directly, I rarely talked to people about absolute specifics of various therapeutics and treatments. However when confronted with the "slashing, burning and poisoning" comment here is the answer that I often used.

Take a look at the two photographs that I have included in this post.  In the photos you will see two cars.  One of them is the 1908 model T Ford - you know the one that Henry Ford said that "you can have in any colour you want - as long as it's black" :). The other is a somewhat more modern version of a Ford GT sports car.  (Disclaimer: I do not own a Ford, and do not have any interest in Ford, but am merely using these pictures for the purposes of illustration.)

Look at the two pictures and ask yourself, "where's the progress?".  No one would have the slightest hesitation in noting the incredible progress that has been made since the very first automobiles were introduced compared to the state of the art today.

And yet, both of these cars still use a version of an internal combustion engine, they both still roll on four rubber tires, and they both still have a mechanical steering device called a steering wheel by which you navigate them.

Where's the progress indeed?

The point is, of course, that just because both cars have engines built upon the same fundamentals, or rubber tires or round steering wheels, we should not be fooled, even for one millisecond, into thinking that there has been no progress. 

So it is with cancer therapeutics.  Just because we are still using surgery, radiation therapy and chemotherapy does not in any way mean that we're still doing things the same way we did 20 or 30 years ago – or for that matter even 5 or 10 years ago!  The advances that research has given us in surgical and radiation techniques are nothing short of remarkable, as we develop and employ more and more precision including laser-guided and computer-guided enhancements.

Research means that chemotherapy of today does not, and certainly chemotherapy of the future will not, resemble the chemotherapy that one had to endure in years past, as we develop more and more selective and more and more targeted therapeutics that attack the cancer cells and leave normal cells alone.

In subsequent posts, I will give you some examples of how we are getting more and more selective and therefore more and more effective in our treatments.  Research has led the way for us to use surgery radiation and chemotherapy in brand-new ways with much better effects and far fewer side effects.

The days of "slashing and burning and poisoning" are done…