Here’s my interpretation of the metaphor used by Aurelio Lorico, a Touro University of Nevada science professor and lead researcher on a groundbreaking cancer drug study, to help a literature major understand his work. Imagine a car carrying important military orders. It arrives at a base to give a unit these orders. But before the car is let in, the driver has to show the guard proper ID. In this scenario, The car represents a packet of information (extracellular vesicle) sent from a cancerous cell into the nucleus of a noncancerous cell (the base), allowing the noncancerous cell (the unit) to be “recruited” to the cancer’s cause. Once that unit is recruited, it helps the cancerous cell recruit many others through the same process, spreading the cancer (metastasis). The driver, guard, and ID represent three proteins required for the car to get into the base, and, thus, the orders to get to the unit. Lorico and his team are developing a drug to zap the ID, so that the car can’t get onto the base — the metastasis is prevented. Beyond patiently and painstakingly explaining this process (thanks, doctor!), Lorico recently discussed with Desert Companion the significance of the work, and what’s next. An edited excerpt of the discussion follows.
Why focus on metastasis, rather than on the cancerous cells themselves?
The main problem for cancer patients is not the cancer itself. It's the metastatic cancer. More than 90 percent of patients that succumb to the disease die because of metastatic cancer. And the truth is that there is a lot of talk about the different types of cancer — breast cancer, melanoma, brain cancer, lung cancer — but the reality is that all of them have in common the metastatic process. So, you don’t die because of the localized breast cancer; you die because of the metastasis to the brain, or to the lungs, or to the liver, and that's the same for essentially every type of cancer. So, for metastasis to take place — and sometimes it takes place after five years or 10 years — it's required that there is an interaction in the metastatic site between the cancer cells that have arrived there and normal cells that we call fibroblasts, or mesenchymal stem cells, or macrophages. And they have to help the cancer cells to establish and form the metastasis.
Scientists have known for some time about this interaction between cancerous cells and noncancerous ones. What you and your team uncovered are specific details of how communications get into the noncancerous cells and, essentially, hack their wiring correct?
Exactly. So, now having discovered this, we have synthesized specific inhibitor molecules of this process. So, when we give this specific molecule, the complex of three proteins does not form the road (the invagination), and the car has nowhere to go. So, we block the communication. Now the metastasis cannot form because this cancer cell no longer has the help it needs from the surrounding cells.
So far, your work has focused on breast and colon cancer and melanoma. Why?
Because we have good models in the laboratory, so that we can prove this theory. And then once we proved it in one type — we started with breast cancer — then we've tried another cancer, melanoma, and it worked, and then we tried another cancer, colon cancer, and it worked as well. So, our feeling is that this happens for every type of cancer.
In theory, in melanoma and breast cancer and colon cancer, they all can send their cells to the lung, right? So once their cells are in the lung, whether they are breast cancer, or melanoma, or colon cancer, they all need to interact with the normal cells. They all need to send their messages into the nucleus of the normal cells. That's why this mechanism and the drugs that block it, they can actually block this phenomenon in multiple cancer types.
Touro received a $275,000 National Institutes of Health grant in 2022 to support your work. Have you received other funding since then?
I have received two more grants from the Touro University system. They were competitive grants, but they were limited to the Touro University System, which is a worldwide system. And they are small grants ($100,000 or less).
Describe that “worldwide system.”
All the experiments have been done at Touro University Nevada. We have collaborators in many other places. The main help in this process has been the Italian collaborators, which, under our guidance, have synthesized the chemical drugs, because we do not have a chemical synthesis lab in Nevada. So, I've instructed them how to build these molecules, and they've done that, and they send us the molecules, and we test them. And then I have a collaborator in Germany that has been working with me more on the theoretical standpoint.
What are the next steps for you and your team? How close are your drugs to public availability?
Nowadays, with the progress in laboratory research, these times can be shortened very much, and also the Food and Drug Administration, if there is a very bad disease, sometimes they can have very shortened time to approval. This being said, we're still some years away in the best-case scenario. But maybe not many years.
Of course, we do not have the proof that these drugs would cure or will help cancer patients. We are in an advanced preclinical stage of development, but we are reporting not only on a new mechanism; we actually have drugs. So, we've done three steps. First, we've discovered a biological mechanism, then we have found the molecular mechanism, and then we have synthesized the drugs that block the biological mechanism, molecular mechanism. Now is drug development.
It seems like a project of that scale would be expensive. How much funding will you need?
It requires millions of dollars, yes. But the very exciting part of this is that this nuclear transport that we have discovered, is not only helping cure cancer metastasis … but the other advantage is that, now that we have discovered this new mechanism of nuclear transport, we've also found that it works for viruses. So with the same drugs, we can actually block many viral infections. And this mechanism of transport is also important in neurodegenerative diseases like Alzheimer's, and others. So, we are working at the same time on these other diseases.
Any other barriers, besides money?
Johns Hopkins is currently testing these drugs in pharmacokinetic models to understand more about them. So, we have collaborations, we're trying to move forward, but Nevada, I think, needs to increase the research capacity, because there is a lot of money around but not a lot of research going on.
