My Tumor MicroEnvironment! What Me, Worry?

It’s bad enough to worry about having had a tumor, but now we are learning that the microenvironment of our own systems–and their microlocations–are important!  What is next?  And what is a tumor microenvironment anyway?

My own primary tumor apparently was quite efficient in spinning off its alien babies, the metastases which peppered my lungs.  None of these ambitious invaders seemed to have found a happy home in my bones, so one could think that my lungs were a nicer neighborhood or microenvironment for my mets.  It is bad enough to have the cancer on the move.  Does this mean that mets in one place will predict mets in another?

To answer this question, it is helpful to understand how cancer cells move through the body and find their new unhappy-making homes.  Happily  for us, as the hosts of these unwanted and busy guests, the body does try hard to limit their invasive moves.  And the presence of our healthy cells and the general brakes of our immune system do offer some protection.  Editorial note here; It wouldn’t hurt one bit if you do everything you can to support your immune system, and make it efficient in keeping you healthy.

For cancers to grow beyond their original location, individual cancer cells have to escape the primary tumor.  Think of tiny ships leaving earth’s atmosphere, pulling away from the tethers of gravity and the support mechanism inherent in the tumor environment. Then those cells must survive the ride through the blood or lymph system, which is really designed to break up the cells, before landing at a new and unknown site.  Cleverly, there may have sent out certain proteins in advance to, to fertilize the ground of that new colony, but the seekers may never find that soft landing.  And then those same cells need to support themselves, far from home.

Researchers tell us that tens of thousands of cancer cells can be shed into circulation every day, but less than 1/100 of one percent of them ever survive to relocate and reproduce.  Lot of good things happen to stop that.  And those darn cancer cells use platelets as shields against the vigilant immune system and recruit clotting mechanisms to strengthen their structures. Some might even take on characteristics of stem cells as camouflage.

Should that tiny colony of cells find fertile ground, they must survive many challenges before they can grow and cause any real impact on our systems.  Researchers and patients are aware that certain cancers seem to have favorite metastatic sites, with lungs and bones the preferred new locations in kidney cancer.  Just to make things more confusing, there are several ways that cancers grow, which seems to depend on the original source of the cancer.  And there are local growth factors, quite normal and appropriate in the bones, which can be subverted into helping establish new metastases.  It’s as if the cells looked around and found local cells ready to collaborate with the enemy!

But that same collaboration and the resources that this unholy partnership brings the new relationship gives an opportunity to prevent the invaders from settling in comfortably.  Noticing the chemical welcome mats, researchers are aware of the possibility of “pulling that rug out from under” the newcomers, and making them less likely to set up shop in your bones or lungs.

They have been especially helpful in preventing bone metastases by using some agents that were developed not as anti-cancer agents, but  to strengthen bones in general.  Since breast cancer also moves to the bones, the use of these agents, bisphosphonates and others, is wide prescribed not only in the presence of mets in the bones, but to prevent them. Prevention of mets is an adjuvant therapy–another of those new words for your vocab test.  Examples of these agents are Zometa and Xgeva, each with special characteristics.

In advanced RCC, where Sutent is being used, there are studies which show longer benefit, when Zometa is also given the patient.  Zometa obviously makes it less comfortable for the mets, which may be tiny and unseen, or newly visible on a bone scan, less likely to continue to grow.  And I am for anything that makes is hard for mets to grow, even if they are really still in the neighborhood.

Just as there are many factors which aid and abet the nasty mets to leave home and travel, and take on new disguises to evade the immune system, there are likely many more approaches to limit the welcome at the new desired location.  One challenge is finding those, as is obvious, and more urgent is to understand when one’s targeted therapy is helping against metastases in one part of the body, only to have a new location be invaded by mets.

If you are getting benefit from one targeted agent, but new mets pop up elsewhere, do you stop the Sutent, and risk more mets in the original area?  Do the new mets need a biopsy to see if there has been a change in molecular characterization which may direct the use of the next medication?  Can you add another agent without undue side effects?  None of these questions have clear answers, but a willingness to examine what it happening and how and where any mets might be made less comfortable in their growth patterns is critical.  Wish it were simple, but it is not.