Detecting cancer, one CTC at a time

In honor of breast cancer awareness month, I've been scouring science headlines around the internet to find really interesting, clever, and unique approaches to fighting all sorts of cancer. I stumbled on some fantastic research this morning that really piqued my interest; I hope it does the same for you! The early diagnosis of cancer makes a dramatic difference in the prognosis of patients. Take, for example, breast cancer. Below is a chart showing 5 year survival rates of breast cancer patients relative to the stage at which the cancer was diagnosed:

Figure 1: The 5-year relative survival rates among breast cancer patients

The contrast between Stage I and IV survival is pretty stark, as you can see! The cause of this jump is a phenomenon known as metastasis, which is cancer's ability to spread its tumors from the primary site to remote organs. In fact, the majority of breast cancer fatalities occur due to these remote tumors (in the bone, liver, etc) rather than solely cancer in the breast. This is a defining feature of Stage IV cancers.

Detecting these metastatic tumors has been a challenge, but recent advances have allowed scientists and clinicians to detect circulating tumor cells (CTCs) in the blood. This allows us to study and monitor cancer in a noninvasive manner, which is critical in ensuring that the cancer treatment process is as painless as possible. Aceto et al. published a paper in Cell describing a very interesting discovery in the nature of these cells. As it turns out, the cells that are the most successful in establishing remote tumors travel in clusters, rather than in isolation.

Figure 2: A schematic showing CTC mediated tumor establishment. Credit: Aceto et al. 2014

These cells express a protein called plakoglobin, a cell adhesion protein which presumably allows the cells to remain in contact with one another until they reach their destination. Traveling in this way seems to provide a protective advantage, as the scientists also noted that solitary tumor cells suffered much higher rates of cell death. Patients with high levels of this protein in their cancer cells had a much shorter metastasis-free survival time.

Researchers hope that with this new knowledge, our monitoring of cancer patients will become much more effective. For example, if a clinician notices that levels of plakoglobin and/or clustered CTCs are rising in his/her patient, that may call for a more aggressive treatment regimen. It may also warrant a closer examination of the genetics of these clusters, as metastatic tumors are notorious for having different genetics than their parent tumors, which may partially explain why some chemotherapies eventually stop working.

For more information, check out the full paper in the first hyperlink above. The more you know!

Using stem cells to treat cancer?

Cancer is a very interesting disease. As I mentioned in a previous blog post, its ability to mutate into countless different forms means that generating effective ways to combat it is no small task. Researchers and physicians usually have to be pretty creative with how they approach treatment- no one drug will help every patient! A very interesting review coming out of Nature talks about a very interesting new way in which scientists are approaching this problem. As was reported by several laboratories, it turns out that stem cells have the natural tendency to migrate towards tumors. Using this principle, biologists are beginning to hijack these stem cells to deliver a wide variety of different things. Here is a brief summary of some of the therapies discussed (for the full story, check out the paper that I linked above!

Figure 1: A colony of stem cells!

Strategy 1: Delivering Therapeutic Proteins

There are many proteins out there that can be used to cause the spontaneous death of cells. One of these proteins is called TRAIL; it binds to a protein called death receptor 4 (ominous, I know!) and causes apoptosis, which is the cells way of destroying itself. By navigating directly to the tumor, stem cells are able to deliver these noxious proteins directly to the cells they wish to kill while sparing the surrounding tissue!

Strategy 2: Stem Cell Mediated Suicide Therapy

In this treatment, stem cells migrate to the tumors of interest and convert a previously harmless drug into one that is pretty nasty! By doing, this the stem cell sacrifices itself while simultaneously preventing the risk of it going on to divide into different things. This also means that dangerous drugs will only appear at the tumor site - if the drug manages to escape and go somewhere else, it won't be toxic because it hasn't been converted any stem cells!

Strategy 3: Nanoparticle delivery

One of the biggest difficulties in getting drugs to their targets is the body's own immune system. Your innate defense system is pretty potent (which is a very good thing!), but it also means that drugs are recognized as foreign entities and are quickly destroyed. To get around this, scientist have begun to surround drugs in nanoparticles, which your body doesn't identify as being a bad thing. This "Trojan horse" method allows your therapeutic of choice to sail past the defenders and make it to the end zone. Touchdown!

Figure 2: What your stem cell friends look like delivering nanoparticles. Close enough, right?

Strategy 4: Oncolytic Virus delivery

Oncolytic viruses are viruses that selectively destroy the rapidly dividing cells characteristic of cancerous tumors. However, the delivery of such viruses is difficult due to the same hiccup described in strategy 3: avoiding host immune defenses. The ability to "hide" within a stem cell allows the virus to remain inconspicuous until the moment is right!

Figure 3: A schematic of the therapies discussed above. Pretty snazzy! Picture courtesy of Nature Reviews Cancer.

But as you may note from the the title of the review, Stem cell-based therapies for cancer treatment: separating hope from hype, not everything is as simple as it seems! The field of stem cell research is still relatively young; thus, there are still a myriad of problems with using stem cells in humans. These issues are too long to list here (contact me if you wish to discuss!), but always take any new revolutionary treatment with a grain of salt. I, however, remain incredibly optimistic that we will circumvent these challenges and that stem cell therapies will soon become routinely used in the clinic!