In this presentation Dr. Dino Prado explains that many solid tumors develop a dense stromal barrier—composed of collagen, hyaluronan, and cancer‑associated fibroblasts (CAFs) activated by signals such as TGF‑β—that acts like a "Great Wall" around the cancer. This barrier physically blocks chemotherapy, targeted agents, and immune cells, resulting in only a few percent of intravenously administered drugs actually reaching the tumor and contributing to treatment resistance, metastasis, and systemic toxicity. Prado argues that standard oncology rarely assesses this barrier, whereas his practice uses advanced spatial biology, imaging, next‑generation sequencing, and immunoprofiling to quantify the fibrous microenvironment. With that information, they employ image‑guided interventional radiology to place hair‑thin catheters directly into the tumor and deliver custom‑designed drug payloads (SIPI/SIPPY – chemo‑immunoprecision injections). This approach both concentrates therapy within the tumor, seals its blood supply, and creates an in‑situ vaccine that re‑activates systemic immunity. A case study of a stage‑4 neuroendocrine carcinoma demonstrates rapid tumor obliteration, disappearance of circulating tumor cells, and marked quality‑of‑life improvement. Prado cites broader data (2024 publication) showing a 35‑fold improvement in response and a 43‑fold increase in quality‑of‑life across 199 late‑stage patients. He emphasizes that the stromal barrier is present in pancreatic, breast, colorectal, gastric, head‑and‑neck, and other cancers, and that overcoming it with precise, locally delivered, molecularly matched therapy is essential for effective oncology.
Chapters
Imagine a castle with a giant wall around it. That wall just keeps the good guys out, keeps out the chemotherapy, the medicine, and even your immune system from coming against your cancer. Many cancers build this real biological wall called a stromal barrier. Today, we're going to talk about the importance of this wall and why it blocks chemotherapy. And most chemotherapy doesn't even make it to the tumor. If you give an IV chemo, maybe 5%, 2% make it. But when you have this fibrous wall, the stromal barrier, it's even worse. But there are smart ways that doctors tumors sometimes putting the medicine right in directly to the tumor. And it's so critically important for so many cancers. In this episode, we're going to bring this right down to the great wall of cancer and how it's blocking treatment, suppressing immunity, and pushing metastasis. And we're going to discuss how to overcome this. Hi, I'm Dr. Dino Prado, founder of Envita Medical centers. For the last 25 years, we've helped patients who didn't get the results they hoped for from major hospitals using the latest technologies and treatments from around the world. And technologies we've developed with deep learning and precision targeting, advanced testing. We've helped patients get individualized plans to cut through the guesswork and guide them to smarter treatment decisions. And so today we're going to start with what is the stromal barrier. So inside tumors, there's more than just cancer cells. There's stroma fibers, gel like material that helps cells when tumors over build this support. It's called a desmoplasia. It's extra thick, tangled scaffolds of collagen and hyaluronan that lays this cancer associated fibroblasts. And so what happens is these fibroblasts are activated by growth signals like inflammatory signals like TGF beta, and then they pile up these proteins and they make the tissue stiff and crowded. And this is really important. Look. According to nature review of cancer in 2020, the consensus statement for these cancer associated fibroblasts, they deposit and they remodel this extracellular matrix and shape that affects the immunity in the tumor, in the tumor microenvironment, meaning it's not letting your immune system get to the cancer. Remember, as I've said many times before, the immune system is the first and last defense. But on top of that, you may be getting chemotherapy that's pushed out partly because of the pressure inside of these stromal barriers, but also because of this fibrous material. And so What I want you to know is one of the things that's important in precision oncology and the work that we do, we test through spatial biology for this composition of stromal barriers. We look for this fibrous tissue by combining imaging, advanced molecular profiling and techniques so that we can actually measure this in our patients. This tells us whether the chemo may not even work because we have to get inside the tumor to make it effective. So this is something that you're not going to see in standard oncology. It's not done in the, in what I call the once size fits all. And it's definitely not an integrative procedure. It's specialized because these tumors, particularly tumors like pancreatic cancers, they're loaded with this fibrous stromal. This is one of the reasons they don't respond well to treatment. And they squeeze the blood vessels, pushing the drugs out so you're not even getting them into the area. It dampens the ability of the immune system to respond. So this has been one of the reasons why pancreatic cancer has issues with getting treatments because of these fibrous tissues. Breast cancer has the same thing. It's a stiff matrix that pushes the cells to grow and spread. So the matri and breast cancer that gets fibrous is pushing the metastases in the spread, weakening the immune system and making the tissue harder and more aggressive. So this is what you see. I mean, this was well published in Cancer Cell, that this is one of the effects of breast cancer, another difficult cancer. With colorectal cancers, you'll sometimes get these immature desmoplastic patterns, these patterns of these fibrous tissue that's laying down wall. And whenever we see that, that's a worse prognosis. But if we can get inside the tumor, which we'll talk about here in a minute, we can change things. Gastric stomach cancers especially also have this. They' known for these hard fibrous tumors. So trying to get chemotherapy to these is not very easy. Also head and neck squamous cancers, these all have these cancer associated fibroblasts that support its ability to spread and become resistant. So we just can't ignore this particular factor. This great wall of cancer exists and so we need to work through it. There are other cancers that have this too. And to the degree that a cancer may or not have this, it's based on testing, understanding whether or not these stromal barriers exist, and then from there, how to approach it. So why these walls stop chemo? How do they do here's the tough truth. When you give chemo by intravenously, by your veins, well about under 5% even makes it to the tumor. So that means the rest of it's going to do what? Weaken your immune system, weaken your healthy cells, weaken your nerves, it destroys tissue. So that's why we don't like that. We don't like all these toxic chemotherapies that destroy your immune system. We want it to get to the tumor. And these stromal barriers, this great wall, as I call it, around the tumor, prevents that from happening. These blood vessels in these tight stromal barriers, they'll squeeze out the chemotherapy so you get less blood flow, less delivery of, less delivery of the immunotherapy. Whatever you're doing isn't getting there. There's the thick collagen, this hyaluronan is called. It's like a fence and it grows and it develops this crowded tissue, blocks the immune system, blocks the medicines from getting there and the immune system shuts down. It also impacts signaling. It's one of the complex things here. They actually can push metastasis because they're so thick. You get this inflammation. It weakens your T cells, the immune system that you need, and it reduces your immune response. So we need to understand these barriers and get over them. The wall makes the hard and is so narrow that medicine and immune system just can't get in there. This is such an overlooked area in oncology and it's so surprising. But I'm going to go over some solutions here in a minute which make a big difference. Breaking the wall and getting the medication right to there into the tumor is critical. One of the ways we do this is using image guided interventional radiology, oncology. We can use a catheter the size of a hair, tiny one, get right into the tumor and now deliver a hundred percent of the medicine. But not just any medicine. Genetic transcriptomic metabolomic ngs, next generation sequencing, immunoprofiling and then delivering those medicines directly into the tumor. You can use technique that we use with direct intertumoral injections, which is like a trans arterial that goes right in there with image guided and you go in and out with a catheter, size of the hair and you're done with a band aid. But now you got it right to the tumor. And this has worked very well for these tumors that are difficult, some that might be in the liver, pancreatic. Then while you're there, you can seal the blood supply of these tumors. Now You've activated the immune system. So not only is it working at the tumor, it starts to work everywhere else in the body. In our work, we call it SIPI chemo immunoprecision injection. Because we have seen time and time again when these fibrous tumors, which by the way, many different cancers can have this. I'll give you a case example here. Stage 4 Fast Growing Neuroendocrine carcinoma. We did scans and you can see the scans of large liver tumors, adrenal tumors, and the chemotherapy just wasn't responding correctly. So what we were able to do is use SIPPY chemo immunoprecision injection with direct image guided. We get in and out, 45 minutes, you're done. With a band aid. We got right to the tumor, CT guided and placed the needle right, that tiny catheter into the tumor, killed the mass in the liver and basically the other lesions and came out. And then you can see in the imaging how it totally cleared, how it effectively just obliterated the tumor. And what happened roughly even four months later, you can see the patient's quality of life improved significantly. The tumors were obliterated. Their circulating tumor cells, which I love to talk about, dropped significantly to zero. That means they had a high number, like 40, it came down to zero. So their methylation score, something else we look at, dropped significantly, meaning the tumor was dying. And not just at the, at the tumor, where these walls of stromal barrier were, but everywhere else in the body because we created an immune system response that goes everywhere. So it's so important to understand that so many cancers can be effectively treated. When you have targeting, you do the right testing, you get the right deep learning around is it fibrous, what's the genetics that need to be done, the immunotherapy done and then get it directly into the tumor. We see just great improvement in many of these cases. So hoping for IV drugs to squeeze through some of these walls isn't going to happen. Pancreatic, a lot of other cancers, sometimes breasts even, you'll see this in other cancer types. NCPI that we've used have brought the medicines right to the inside of the tumor, localizing, concentrating it and basically killing the tumor, shunning the blood supply and then creating what we call an in situ vaccine, which describes basically an immunotherapy reaction happening throughout the tumor. And in 2024 we published 35 fold improvement in compared to standard oncology. Over 199 patients we treated with late stage cancer and a 43 times improvement in quality of life. So part of our algorithms for that was sippy, the targeting of the drug, first of all, seeing if the patient needed it, secondly, custom building the drug and then delivering it, as I call the payload, right into the tumor, sealing the blood supply and coming out. And our team is fantastic at this. You know, we're doing this for years and being able to do this throughout the entire body, not just in one area. Because if you look at interventional radiology, oncology might do the liver, but not even with targeted drugs. They might just put in standard chemo and the drug selections make a huge difference in the chemo, immunoprecision injections. One of the things that we found in that platform is the drugs are really important. They have to be targeted, they have to be delivered with a micro catheter and they have to be custom designed. You just can't put standard chemo in because you need to know whether their DNA and RNA targets, immune profiling is all being matched to get the best outcome. So the spatial thinking inside the tumor is where the key happens. That means inside this tumor you have the immune cells that are all near each other, like neighborhoods, blocking the immune system fighting. And the goal here is to unblock it. So now the immune system throughout the body can find the cancer, go after the micrometastases using an immune system response and treat the patient. So it's not uncommon that we would treat one area of the body and see another area shrink just by treating that area. Because now the immune system is able to go systemically around the body and kill the micro metastatic cancer cells. If you look at this for a second, the stiffness of these cancer walls, this cross linking of collagen and it affects growth, metastases, weakening of the immune system. To overlook this makes no sen, because if you do that, your IV chemo isn't going to work. But what it will do is weaken your immune system. It'll cause more mutations, more resistance, kill healthy tissue, kill your nervous system, lose your hair, feel fatigue. This is why we're able to avoid a lot of that in the, in the strategies. When we understand that tumor has a wall and we can get into the tumor, it's going to make a big difference. This technique is critical as a part of immunotherapy because even if you have great immunotherapy, but you can't get into the tumor to the tumor, you're just not going to get the response you want long term. So this is what we call the Great Wall of Cancer as a way to teach this. But you can overcome this and get of the treatment right where you want it and guided through interventional radiology, oncology and deliver drugs that are specific. Not general drugs with loaded on beads, but specific drugs that are customized for you the patient. So I hope this was helpful because once you understand that a lot of cancers have this fibrous barrier, you can understand why they're not responding to treatment. And if you can overcome that barrier, you can start to improve the response. I hope this was helpful for you. May the Lord bless you on your journey to healing. Bum bum bum bum bum bum bum bum bum bum bum bum bum bum bum.
