The Stromal Barrier Problem: Why Chemo Fails for Pancreatic Cancer (And What Works)

Today we're cracking the code on pancreatic cancer, one of the most difficult ones. Using precision oncology, understanding the differences from early stage to late stage pancreatic cancer. What if we could slip past the brick wall stroma of the pancreatic cancer, reach the tumor with 3D and kill it from the inside, prime the immune system with the purpose of tracking down all the cancer cells and win with a liquid biopsy while avoiding many of the brutal complications and side effects that you can see with Whipple procedures and early stage disease. And for sure, late stage disease therapies seem to work too well. I'm Dr. Dino Prado and today we're going to talk about less guesswork and more life in pancreatic cancer. For the last 25 years, my team and I have helped patients who failed the top cancer hospitals across the United States. Today I'm going to show you some targeted ideas that we use immune centric path. That's a total contrast from the old cut, poison and burn playbook with a modern plan, advanced mapping. We're going to talk about pancreatic cancer and think about how we're going to map this using next generation sequencing the DNA transcriptomics, RNA and immune spatial biology, which is really important here where we can the tumor from a 3D perspective. And then we're going to talk about how do we get to the tumor very elegantly using 3D cone beam interventional radiology oncology with targeted drugs and immunotherapy direct to tumor. So that we not only get a kill at the pancreatic cancer level, but we get a systemic response if the cancer has already spread. And this is designed to be immune centric. It's very different than the current standard of care model. So why is the old playbook struggling with pancreatic cancers and Whipple procedures? It can be life saving for some patients, but it's a massive surgery with high complication rates, rates even in reputable centers, pancreatic fistulas, delayed gastric emptying, infections, diabetes. So it has a high morbidity rate of 40 to 60% range and a preoperative mortality of still 2 to 10% depending on the volume, recovery is long and the quality of life not very good. Then from there that's the Whipple procedure. Pancreatic cancer patients can do systemic high dose chemotherapy which has a ton of problems. One, most of it doesn't even make it to the tumor because pancreatic cancers have these dense stromal barriers. So maybe 0.07 or 1% even make it to the tumor because of the high pressure within those tumors. So this is a problem pancreatic cancer. So only a tiny fraction gets to it. And that's even if it's the right selected chemo. See, pancreatic cancers have these desmoplasias that are notorious for blocking delivery. That's like trying to water a tree through concrete. It's very hard to get there. So we're going to try to overcome this with the precision that we're going to be talking about today. A more intelligent way of overcoming this. The outcome reality in pancreatic cancer is difficult because even our best multi drug regimens that exist right now and standard oncology you have a maybe median survival of 10 to 11 months. That's not good. And depending on the fitness of the patient or the regimen of the care. So we can do much better than that. And I'm going to share with you how we do that. We use precision oncology. I'm going to get into that in a moment. But we need to look at changing the model because it's just not giving us what we want. And that's according to JAMA Network oncology. Those are not my opinions clinically. Any doctor that works in the space of oncology knows pancreatic is one of the more difficult cancers. But I think it's because we're going about it all wrong. And I'll show you a technique that's been helpful for several of our patients. The goal is to change the script this complicated and difficult cancer to treat. So let me show you what has helped our patients. Okay, here's a side by side. You have the whipple that equals big incisions to the abdomen, plumbing, rerouting stomach, pancreas, intestines. That's just a lot versus using image guided 3D cone beam where we can see all the vessels in the tumor. Go in with a catheter the size of a hair with a genetic targeted chemotherapy and immunotherapy, deliver it into the tumor of the pancreas, seal the blood supply and come out with a micro catheter and you're done with the band. It is just Star wars compared to what we're seeing in standard oncology. It's clean. It allows us to get to the tumor, kill the tumor and create a systemic immune response throughout the body. So how does precision look different? Well, first we start with mapping because before we deliver anything or any treatment, we want to start with deep mapping. So we start with next generation sequencing. Think of this as the DNA. So I always like to use the analogy a drone in the sky and we can see down below the driver in the car, that's the DNA. It shows us what are the mutations and the resistances to this cancer. So we need to address those. The problem is when you run DNA might find 500 plus genes, but there aren't many drugs that affect those mutations. So we now need to look at not just what's available on label approved FDA drugs for pancreatic, but off label and repurposed drugs which are drugs that are used for something else, but the mechanism is perfect for your cancer. And then phytotherapeutics and nanoparticles so we can get those involved, get the plants there so they can do their work and immunotherapy all combined based on these mutations. Then you add transcriptomics, which is the rna, another thousand plus markers. And this is important because it shows us all the roads and all the ways that the cancer can evade treatment and we can block those, including getting the immune system involved and helping the treatments work better. And finally, the most important part is immune spatial biology. This helps us look at the gangs that are blocking the tumor and let the police of your immune system get in the T cells macrophages so we can get past the stromal barriers and get to the tumor. So now we're looking at 1 plus 1 equaling 11 because we've got a lot of data, we see a lot of resistance and now we go in with 3D cone beam and as we go direct to the tumor, we kill the cancer and we create a systemic immune respons. Now that's just part of the story. It's still powerful in my opinion, clinically, many times better than the Whipple procedure. Without all the complications of basically rewiring all your intestinal parts. Right. This is much more elegant. But in addition to that, it's the systemic immunotherapy that's important because at the end of the day, if a patient with pancreatic cancer has a chance for long term remission, it's also because their immune system is intact and it's able to go after the cancer and kill it. So alongside we look at the modeling in the immune system. So we have all this data. Now when you compare this to standard of care where all you have is immune imaging, tumor markers and a biopsy and then the national comprehensive cancer network guidelines, there's a one size fits all model for pancreatic cancer. The problem with that is two pancreatic Cancers of the same type and stage have totally different treatments because when we do the deep mapping, we see all the markers and each one is different, so there's heterogenicity. These two cancers are unique, so treating them the same is really not the way to go. What you want is targeted care. So once we have this data now we can plan the care with precision. We can build the medicines, we can build the immune system, we can even do chemotherapy systemically because if we have cells that have metastasized past the pancreas, we can kill those using genetically targeted fractionated chemotherapy. The same genetic and immunotherapy information that we use direct to tumor can be modified to be used systemically intravenously with microdoses so we don't have the side effects of hair loss, fatigue and low white blood cells. Instead, we can have energy throughout care and improve the quality of life. And that's really important with pancreatic cancer. Now let's add the integrative treatments that are important here. So we have phytotherapeutics. So let's say there's a lot of inflammation and we have markers for inflammation, then we have the that fight against that at an intravenous level. Even in a simple study that showed vitamin C helped extend life for pancreatic cancer patients. About 70 people in the study just using high dose vitamin C. But that may or may not be the right target for you because it depends on your molecular markers of which integrative agents are going to support the care the best at. The key of all of this is like I said in the beginning, it's an immunogenic treatment. We need to not just kill the tumor, ablate it, shut the blood supply down, but we need to release the new antigens and we need to release the damps, the damage associated molecular patterns. Because once your immune system is aware of the cancer, it can now fight it elsewhere. So you can now start to see the elegance of precision oncology. And you might ask, how do you know if this is gonna work or not? Because we measure it as soon as we're doing care through the care process. Pancreatic cancer is considered one of the dirty cancers because it mutates quickly. It can mutate pretty quickly later stage pancreatic cancer. So we monitor it with CT free DNA, circulating tumor cells, methylation scores to help confirm that treatment is working. If we see a change in response not going the way we want, we those cocktails, those medicines that are made based on the DNA, RNA and immune profiling and go back in because we're ahead of the curve. We're not waiting for a tumor to reappear. We know the response is working or not. So this is important because it's like a dashboard to helping us monitor the whole treatment process. And it's really simple. All we need is a blood test and it gives us this data. And of course, as a patient's responding, we follow with imaging and tumor markers and other things. But the real key here to getting at the tumor directly is the 3D cone beam. This is an interventional radiology oncology procedure where you lay down and you can see with 3D imaging, the pancreas. You can see all the blood supply going to the tumor with high, high level precision. And you get right to the belly of the beast, shut it down, kill it, and about 45 minutes later, maybe an hour later, come out with a band aid. That's the precision that is really powerful here. Where NCCNN guidelines are a little bit different, they're going to recommend Whipple's, which is an option for patients in early stage pancreatic, but it also comes with its potential side effects and quality of life issues. In addition to a Whipple is not even an option if the patient's pancreatic cancer is already spread beyond the pancreas. They're going to use a standard system regimen to treat that tumor without having all the detailed markers based on what that patient needs and to be able to custom build an immune system program for that pancreatic cancer. So this is why we need to see exactly what you need through personalized testing. First, build the map and the treatment plan and then go in with precision. In my opinion, this is how we're going to get rid of pancreatic cancer. Because as we get better with the drug targeting, better with the immunotherapies, we can get right to the tumor, get in and out, treat it at the origin of the problem, and get rid of the cancer using a systemic response. That's the goal of therapy. Now this is different because this is n of 1. What does that mean? It's custom built for the individual patient, not for everybody. Every patient's going to be different. The drug regimens are different, the protocol is going to be different. So let me give you a story so you can kind of see this, how this would work, as we've seen over the years in a live patient. So Joe has pancreatic cancer. Now, remember, it depends on how advanced it is, because the more advanced, the more care involved, the Less advanced, the less care involved. But the monitoring is similar. So this patient has a high elevated C99 PET scans lighting up. You have some distance spread going on and we need to get to the tumor. So when we get the next generation, sequencing, RNA transcriptomics, immunospatial biology, now we know all the actionable pathways now in the pharmacy can custom build the immune centric care and go after the tumor's microenvironment as well. So now using interventional radiology oncology, the 3D cone beam, we're able to go into the tumor with a micro catheter focal right to the tumor, right at the lesion, aiming to kill it and create a systemic immune response. So we spare the healthy tissue. And now and alongside that we have a systemic care of genetically targeted fractionated chemotherapy to go after all the micro metastatic cancer cells along with a toggless adoptive immunotherapy which are the natural killer cells and dendritic cells that are all based on the dams, the damage associated molecular patterns to go after all the micro mets. So what's the goal here? We've taken the tumor out, things are starting to improve and we're systemically treating the patient. And we've lengthened the life and the quality of life of Joe because of this technology. And we monitor him using CT free DNA, circulating tumor cells and methylation scores, which is a simple blood test so we can tell if the treatment's working or not, that we to hold the remission and keep the quality of life. The bowels are stable, the systemic health is fine. That's the difference. So the power precision oncology allows us to walk the patient through this type of care and keep their bodily functions and everything else nice as much as we can. Because we're not doing the Whipple, we're not surgically removing everything and we're not trying to rewire the gastrointestinal tract. It simplifies that. At the same time we're teaching the body how to fight the cancer because there's an immune system problem. Otherwise the cancers can come back and become more difficult to treat. Then there are stromal barriers which are very common in pancreatic cancer. This is why the 3D cone beam interventional radiology oncology works well because we go right into the tumors. We don't have to worry about whether the medicine is going to penetrate or not because we're delivering it directly to the tumor. If you're just doing IV chemotherapy standard, you're only going to get maybe 0.7% absorption to the tumor. So these are some of the problems in pancreatic cancer that we overcome with precision oncology. Now, I want to make it clear that not every patient responds perfectly or the way that we want them to because they can have other complications. But in my clinical experience, our patients always do far better. And when I say far better, I mean that considerably better than they do in standard of care. And we've had some cases that do beautifully. The sooner the better. And it has a lot to do with the planning. This helps you to understand what's going on with these cancers. Think about pancreatic cancer. It's hard to treat for multiple reasons. The location, trying to get the medicines to the area, also trying to handle the spread of the cancer because pancreatic cancer is notorious for being resistant to chemotherapy. So this is why getting direct to tumor is really important and why getting the immune system on board is important and having the right planning with NGS transcriptomics and immune spatial biology. I hope this was helpful. There's a lot I went through, but I just want you to understand that the more precision you have, the better chance you have of responding to care with microdose genetically targeted care and immune centric care to the tumor. Even with modern chemo, metastatic pancreatic survival is still measured in months, not years. And precision doesn't guarantee a cure. But it does give us a smarter play, more targeting, fewer collateral hits, and a far better chance of helping our patients. Patients reach their goal. Precision is not hype. It's elegant planning, elegant delivery. Meeting the pancreatic cancer patient right where they're at, giving them the care that they need so that the cancer has a better chance of responding. I hope this was helpful. As we discussed other options with the treatment of precision pancreatic cancer. May the lord bless you on your journey to healing. Bump.