Hosts
Derek Thompson
Derek ThompsonAbout the episode
Cancer is not a singular disease but a category of hundreds, even thousands, of rare diseases with different molecular signatures and genetic roots. Cancer scientists are looking for a thousand perfect keys to pick a thousand stubborn locks. Today’s episode is about the hardest lock of them all: pancreatic cancer.
Cancer’s power lives in its camouflage. The immune system is often compared to a military search and destroy operation, with our T cells serving as the expert snipers, hunting down antigens and taking them out. But cancer kills so many of us because it looks so much like us. Pancreatic cancer is so deadly in part because it’s expert at hiding itself from the immune system.
Now, here’s the good news. This might be the brightest moment for progress in pancreatic cancer research in decades—and possibly ever. In the past few years, scientists have developed new drugs that target the key gene mutation responsible for out of control cell growth. Recently, a team of scientists at Oregon Health and Science University claimed to have developed a blood test that is 85 percent accurate at early-stage detection of pancreatic cancer, which is absolutely critical given how advanced the cancer is by the time it’s typically caught.
And last month, a research center at Memorial Sloan Kettering published a truly extraordinary paper. Using mRNA technology similar to the COVID vaccines, a team of scientists designed a personalized therapy to buff up the immune systems of people with pancreatic cancer. Patients who responded to the treatment saw results that boggle the mind: 75 percent were cancer-free three years after their initial treatment. Not just alive, which would be its own minor miracle. But cancer-free. The mRNA vaccine, administered within a regimen of standard drugs, stood up to the deadliest cancer of them all and won. Today’s guest is the head of that research center, the surgical oncologist Vinod Balachandran.
The concept of a personalized cancer vaccine is still unproven at scale. But if it works, the potential is enormous. But again: Cancer does not exist, as a singular disease. Cancer is a category of rare diseases, many of which are exquisitely specific to the molecular mosaic of the patient. Cancers are personal. Perhaps in a few years, our cures for cancers will be equally personalized.
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Links:
Cancer vaccine paper: https://www.nature.com/articles/s41586-024-08508-4
P.S. Derek wrote a new book! It’s called Abundance, and it’s about an optimistic vision for politics, science, and technology that gets America building again. Buy it here: https://www.simonandschuster.com/books/Abundance/Ezra-Klein/9781668023488.
Plus: If you live in Seattle, Atlanta, or the Raleigh-Durham-Chapel Hill area, Derek is coming your way in March! See him live at book events in your city. Tickets here: the Abundance book tour
Summary
In the following excerpt, Vinod Balachandran explains to Derek what the typical course of treatment is for cancer and why advancements in those therapies have not been as effective at treating pancreatic cancer.
Derek Thompson: I’d love you to help me understand why pancreatic cancer is so lethal from the perspective of an oncologist. So we have thrown billions and billions of dollars into cancer research and clinical trials, and pancreatic cancer deaths are just going up. Why has the scientific cavalry failed to make a dent in this cancer?
Vinod Balachandran: As you know, pancreatic cancer is now the second-leading cause of cancer death in the United States. So more cancer deaths from pancreatic cancer than many of the other common cancers such as breast cancer, prostate cancer, ovarian cancer, melanoma. [It’s] second only to lung cancer. The survival rates for pancreatic cancer in 2025 remain only approximately 10 percent at five years with our best current treatments, which include surgery, chemotherapy, and radiation. And one of the challenges has been that we’ve had, over the past several decades, many waves of improvements in oncology with waves of oncology drugs, starting with the chemotherapies; and, following that, the targeted therapies; and, more recently, the immune therapies. All of these drugs have had greater impacts on many of these other more common cancers, leading to improvements in outcome, but I think less so for pancreatic cancer.
Thompson: Let’s tell this story then. In oncology, you have these waves of treatment as you describe them: chemotherapy, then targeted therapy, then immunotherapy. I think most people know about chemotherapy, but pick up the story there. What are targeted therapy and immunotherapy, and how have those frontiers failed in the quest to take on pancreatic cancer?
Balachandran: After chemotherapy, the next wave of therapy that led to improvements in outcomes for cancer patients was targeted therapy. So this idea that cancers arise from a break in the DNA or a mutation, and this mutation causes a normal cell to become cancerous and then start dividing and replicating uncontrollably. So if you can develop a medicine that selectively blocks the proteins made by this mutation, you can selectively block or kill the cancer cell without affecting the normal cells, thereby having less side effects. And this approach has been very successful in many other cancer types. In pancreatic cancer, when we tried to apply this principle, one challenge was the mutation that causes pancreatic cancer to form in the first place—this protein gene called KRAS, which for many years has been one of the more challenging genetic mutations to, in fact, block.
So when targeted therapies arose and were making waves of improvement in other cancers, we had still not discovered a way to apply targeted therapy specifically for pancreatic cancer. So we were lagging behind. After targeted therapies, the next wave of cancer treatments were focused on harnessing our own immune systems to fight cancer. And the first way scientists and physicians discovered to do this was through the development of a class of drugs called immune checkpoint inhibitors. So these drugs work by boosting immune systems that recognize patients’ cancers at baseline. So it’s built on the premise that the immune system can recognize cancer enough but perhaps not strong enough in people. And by boosting these immune cells that recognize patients’ cancers with drugs, you can further arm and expand the immune system to recognize patients’ cancers. So [it’s] supercharging your body’s natural immune recognition of cancer. Now, this class of medicines was very successful in some cancers—for example, melanoma, lung cancer—but has not been successful in pancreatic cancer.
This excerpt has been edited and condensed.
Host: Derek Thompson
Guest: Vinod Balachandran
Producer: Devon Baroldi