Taking advantage of cancer’s ability to adapt and survive
Cancer is the second leading cause of death globally, and while a lot of progress has been made, still in 2017, an estimated nine million people still lost their lives to cancer.
I keep asking myself, “Why on earth do we not have a cure for cancer yet?” I mean, it can’t be that difficult, right? I didn’t always want to try to cure cancer. I was actually a plant geneticist, but the black box that was cancer, the unknown, and the possibility of discovering something that might be able to help someone suffering from this disease drew me.
And of course, with a youthful naïve arrogance, I thought I would be the one to cure cancer. My path started by joining the Ph.D. program at UT Southwestern Medical Center in Dallas.
I had this, to me, very simple theory that all you needed to do was find something unique about cancer that you could target and kill that cancer. But while I was there, I came face to face with radiation resistant breast cancer.
Radiation resistant. Basically a ballistic missile that blasts through the DNA, shredding it, and yet, these cancer cells persist. In fact, just about every drug I tried to throw at these cancer cells, these tumors adapted and eventually became resistant, and persisted.
Another way that these tumors can adapt is through metastasizing, and unfortunately, sometimes they would metastasize to the brain. It turns out that the brain is very rich in growth hormones, which cancer loves, and, it’s rich in fat, lots and lots of fat, which basically gives the tumor all the energy it could possibly want.
My curiosity consumed me, and I started reading dozens and dozens of papers daily. One paper in particular struck my eye. It was published by a group at the Salk Institute, by Doctors Soda and Verma. You see, they were trying to understand, how does brain cancer become resistant to treatment as well?
And in particular, one of the drugs used to treat brain cancer patients is called Avastin. The way Avastin works is it cuts off the normal blood supply that feeds the tumors. The idea was that the tumor couldn’t eat, and it would starve and die.
But, with human patients in the clinic, the tumors, when they were treated with this drug, initially shrink, but then over time, those tumors came back. And just like we’re all seeing in the field, these tumors became resistant to that drug.
So the Verma lab wanted to figure out how on earth this could happen. So, they modeled glioblastoma in the lab, no easy feat. One really cool thing that they did, is they basically tagged those cancer cells with a green fluorescent protein. So everywhere those cancer cells went, they could track them.
They then treated these mice the exact same way that human patients are being treated in the clinic. They got the equivalent form of Avastin, and just like with the human patients, those tumors were shrinking, but then eventually came back resistant to the drug.
They took a look inside those tumors, and they saw blood vessels inside those tumors. There should not have been any blood vessels feeding those tumors. They took an even closer look. Those blood vessels were glowing green. They were glowing green. What this means is that the cancer cells, when they were starving, the way they adapted is they turned themselves into blood vessels so they could continue feeding from the blood.
As if that didn’t blow my mind enough, these glowing green blood vessels conveniently, inconveniently for us, lacked the very protein that Avastin targeted, which is why they were resistant to the drug. I was just blown away by this research. I knew I had to join their team. I wanted to figure out how on earth this was happening and figure out a way to stop the cancer from adapting.
So my husband and I migrated from Dallas, Texas to San Diego, California.
And I had a very simple hypothesis again. I’m going to purify these tumor-turned blood vessel cells, I’m going to find their weakness, and I’m going to figure out how to prevent the cancer from turning itself into blood vessels.
Because I thought, well, if I can figure out how to block the cancer from getting food that way, and co-treat with the other drug that prevents the normal blood vessels from coming in, then for sure the cancer would die.
Fast forward three and a half years. Taxpayer dollars, some amazing collaborations, and an institute full of the most cutting-edge technology that I could find. We did it. We figured out how the cancer could convert its cancer cells into blood vessel cells.
So now, here’s the moment we’ve all been dreaming of. We prevent the cancer from adapting and turning itself into blood vessels, and we co-treat with the drug that cuts off the normal blood supply. So for sure, that cancer will starve, and it will die.
Well, guess what happened? I’ll give you a little hint. When you all go home, and there’s no food in your refrigerator, what do you do? You probably go out to eat, or you go to the grocery store.
And guess what the cancer did? It pinched off pieces of tumor and migrated through the brain until it could find other blood vessels to attach to and grow. I made the cancer hyper-invasive. I made it much, much worse.
This was an epic fail. And I’m not going to lie, it was a career contemplating fail. My plan B, at this point in time, was sounding really good, which was to leave this whole research thing all together and go make chocolates for a living.
You see, everything I knew did not contain the answer. We all come to these forks in the road. Okay, let’s be honest. This was more like an entire road closure. I mean, the bridge was just swept away in the flood. But, we have to figure out where the detour signs are so that we can keep moving forward.
Up until now, I was trying to find unique things about cancer so that I could try to kill the cancer, but it wasn’t working, for me. The tunnel vision, the smaller picture, wasn’t working. I needed a bigger picture. I needed to take a step back from my research.
I began to start interesting conversations with my colleagues studying vastly different fields than my own. I was learning about autism, I was learning about schizophrenia, I was learning about depression, cystic fibrosis. I attended stem cell conferences, even neuroscience seminars. I started to see the human body and disease with a wide lens. The tunnel vision, I stepped out of it. The blinders came off.
On one of my detours, I learned some pretty cool things about stem cells. Now we all know that stem cells have this incredible ability to become just about any cell in the body. But, I learned that stem cells have other super powers.
One of the super powers is that they have incredibly loose DNA, which allows embryos to be able to adapt and change its DNA, so that it can be ready for the environment it’s about to come into.
Another super power of stem cells is they are invisible to the immune system – another way that the embryo survives being in the host, so that the host’s immune system does not attack it. And not to mention the very high doubling rate, and the altered metabolism.
Some of these things started to sound awfully familiar to something I knew really well, cancer. In fact, cancer researchers have been discussing these cancer stem cells for decades. But there’s a lot of us that are starting to see cancer as a reawakening of this embryonic stem cell signature.
So what on earth do I mean by that? So we have the sperm and the egg. They come together, and it makes stem cells, and these stem cells multiply and multiply and multiply, until they’re given the command to become a heart cell, a lung cell, a liver cell, a brain cell.
Now let’s look at cancer. So if the idea is that cancer is the reawakening of stem cell genes, all it takes is one cell to wake up one day and suddenly think it’s a stem cell.
So what do stem cells do? They multiply and multiply and multiply until they’re given the “awake.” The cancer cells are multiplying, but in the adult, there is no command to tell these stem cells what to become.
What if, when the cancer cells were starving, and they converted themselves into blood vessel cells, what if they got the command that the cancer was craving the entire time? What if these cancer stem cells were suddenly told to turn into another cell?
So then I thought, maybe I shouldn’t try killing cancer directly. What if I just converted the entire tumor into a bunch of blood vessels? At least that way it wouldn’t be cancer.
But then the nightmares consumed me. I kept thinking, “I’m just going to create a bunch of blood vessels on the brain, it’s going to cause bleeding, and it’s going to be epic fail number… I lost count.”
But, about that same time that I was having those nightmares, an interesting accidental discovery happened. It turns out that when these cancer cells turned themselves into blood vessels, there was evidence that the immune system can now see them.
This means that the cancer cells, when they turned into the blood vessels, they lost their superpower of invisibility. So it is my hope, that if I convert the entire tumor into a bunch of blood vessels, and stop trying to kill cancer directly, that the human body and this magnificent machine inside us will clear the cancer for us.
And if you think about it, in the history of medicine, what else do we kill? We kill bacteria, viruses, yeast. The common theme in all of these, is that they are foreign invaders to our bodies.
But cancer is not a foreign invader, it is part of our own bodies that has become sick. So maybe, instead of killing cancer directly, I can just convert the entire tumor to these blood vessel-like cells, and along the way, cancer can clear cancer for us. The body can clear the cancer for us.
Have I cured cancer? No, but I have formed a theory. One that should be tested by others based off of a lot of failures, but some really interesting pieces of data that just make you go, “Hmmm.”
And this is built off of generations and generations of scientists before me, and even those that, right at this minute, are in the labs trying to put an end to people losing their lives to cancer. Sometimes problems are not as easy as we once thought they were to solve.
We come to these forks in our path, or if you’re in my case, you come against entire road closures, and you have to start looking for detour signs.
But it is important that we continue moving forward, and in doing so, we must begin to seek out information outside of our immediate fields. We must collaborate, engage and try new things.
In doing this, I have been able to form a hypothesis of turning the cancer into a defined cell type, removing the super powers of the cancer so that the body has a fighting chance to take care of cancer for us.
I have started to see cancer as not an invader to our body, but instead a part of our body that is out of sync with our health. Now the challenge becomes, how do we put this part of our body our body, back into alignment?
A theory that I believe can traverse into many other human ailments, including metabolic diseases, sleep disorders, microbiome dysfunction, and even neurodegenerative diseases.
My path continues. Whatever problems you are trying to solve in your life, take off the blinders. Try to look at the problem through your inner scientist wide-angle lens. Collaborate. Engage. And keep moving forward.
And above all, enjoy this nonlinear journey of discovery with me. And if we’re lucky, maybe we discover something, that can help someone, someday soon.