Nothing Could Put a Dent in Pancreatic Cancer. Until Now. (w/ Zeke Emanuel) - The Bulwark

Summary4 min read

Episode Overview

Theme:
This episode of The Bulwark ("Nothing Could Put a Dent in Pancreatic Cancer. Until Now.") centers on a groundbreaking development in the treatment of pancreatic cancer—a disease notorious for its lethality and resistance to effective therapies. Host Jonathan Cohn interviews oncologist, bioethicist, and University of Pennsylvania Vice Provost Zeke Emanuel to unpack the implications of recent clinical trial results, the scientific foundation behind them, and what this means for patients, researchers, and the broader medical landscape.

Key Discussion Points & Insights

1. The Grim Reality of Pancreatic Cancer

Statistics & Lethality
- Pancreatic cancer is the third leading cause of cancer death in the US, with approximately 70,000 new cases and over 50,000 deaths annually.
- The high mortality is largely because it is typically discovered only after it has already spread, at which point no cure exists and disease progression is often rapid.
“So roughly the way to think about it: about 70,000 people get...Americans get pancreatic cancer each year. More than 50,000, 52, 53,000 die...that tells you it’s pretty deadly.”
— Zeke Emanuel [01:16]
- Survival rates have been dismal, with less than 15% living past five years.
- Current chemotherapy options are marginally effective and come with severe side effects.

2. Why Has Progress Been So Slow?

The Genetic Challenge: Ras Mutations
- Pancreatic cancer is driven in most cases by a Ras mutation—a family of genes that signals cells to divide.
- The Ras mutation essentially becomes a stuck "divide" signal, causing uncontrolled cell proliferation.
“And the big problem in pancreatic cancer is that the Ras mutation is turned on. So it just says: divide, divide, divide...And you can’t turn it off.”
— Zeke Emanuel [02:53]
- The Ras mutation has for decades been labeled "undruggable" because no effective means of blocking or interfering with this pathway had been found.

3. The Breakthrough: New Drug Targeting Ras

Scientific Leap
- Recent research has found ways to indirectly or directly target the Ras pathway—using multiple approaches combined for a synergistic effect.
- The new medicines can "deactivate" the Ras gene and thus slow or stop cancer cell proliferation.
- A crucial and surprising factor: the drug accumulates specifically in cancer cells, not in normal cells.
"One of the interesting things about this new drug is that it actually accumulates in the cancer. And so the effect on other cells is way, way less...That’s a big additional advantage.”
— Zeke Emanuel [04:24]

4. Side Effects and Patient Impact

Major Improvement in Tolerability
- Traditional chemotherapy causes widespread side effects because it affects both cancerous and healthy cells.
- The new treatment is much gentler, with "grade one or two" side effects (i.e., mild to moderate), as opposed to the severe, often life-threatening toxicity ("grade three or four") seen with chemo.
- For patients, this means the treatment is not only more effective but also dramatically easier to tolerate.
“One of the surprising things certainly to a regular oncologist is how few serious side effects there were...that means it’s very tolerable. So you’ve got this bad disease with a very tolerable and really much more effective therapy. That’s a kind of winning combination...”
— Zeke Emanuel [05:10]
- Notably, the treatment has already made headlines, with prominent individuals like Ben Sasse reportedly participating in or benefiting from the therapy.

Notable Quotes & Memorable Moments

On the Emotional Impact in the Oncology Community:

“We used to just sort of shake your head. Another patient with pancreatic cancer, less than 15% of people live for five years. And the chemos just don’t work against it.”
— Zeke Emanuel [02:28]
On Old vs. New Approaches:

“That is a response of chemotherapy not targeting the cancer, but targeting all these other normal cells and causing them to die as well. That’s the cost we take for the chemotherapy affecting the cancer. One of the interesting things about this new drug is that it actually accumulates in the cancer.”
— Zeke Emanuel [04:24]
Personal Touch:
Emanuel shares a personal story about a friend, Leonard Shaffer, whose cancer was found incidentally and cured—underscoring the rarity of such good fortune with existing treatments and the need for better solutions.
— [01:57]
Host Encouragement:

“No, no, no, this is interesting. Keep going.”
— Jonathan Cohn [04:23]

Important Timestamps

[00:00–01:09] — Introduction of the episode, background on pancreatic cancer, and Zeke Emanuel
[01:09–02:14] — Overview of pancreatic cancer’s deadliness, statistics, and anecdotal story
[02:14–04:23] — Scientific explanation of the Ras mutation and why it’s been so challenging to treat
[04:23–05:50] — Description of the breakthrough therapy, its mechanism, and its dramatically improved safety and side effect profile

Additional Notes

Emanuel references the broader medical research ecosystem, waving at its vulnerability (especially “what’s happening to it under the Trump administration”—though this specific discussion occurs later in the episode beyond the provided transcript).
Host and guest maintain an informative, optimistic, and accessible tone, balancing technical detail with public relevance.

This summary provides a comprehensive overview of the scientific, clinical, and personal implications of the recent pancreatic cancer breakthrough as discussed by Jonathan Cohn and Zeke Emanuel. The episode stands as both a moment of hope for cancer patients and an illustration of ongoing scientific innovation.

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Transcript11 lines

[00:00]
A
Hey, everybody. Welcome back to Bulwark Takes. I am Jonathan Cohn here. We've had some really big news from the world of medicine. A major breakthrough in the treatment of pancreatic cancer. I've been covering medicine and healthcare for a long time. Really the reaction to this discovery and this trial results. We're about to hear about one of the more pronounced and celebratory reactions I've seen to a research development in recent years. So what is all this fuss about? What does this breakthrough really mean? What doesn't it mean? And what does it say about the system we have, the ecosystem for promoting this kind of research and what's happening to it under the Trump administration? Our guest today is uniquely positioned to talk about these things. It's Zeke Emanuel. You may know him. He's written for the Bulwark before. He's also a vice provost at the University of Pennsylvania, author of a new book called Eat yout Ice Cream. Most relevant for this discussion. He's also an oncologist, so he knows all about cancer and cancer research. He's been at the National Institutes of Health. Zeke, welcome. Thanks for making time for us to talk about this.
[01:07]
B
Great. Thank you for having me.
[01:09]
A
So, real quick, pancreatic cancer 101, I mean, it kills, I think, more than 50,000Americans a year.
[01:16]
B
Yeah, it's the third largest killer. So roughly the way to think about it, about 70,000 people get. Americans get pancreatic cancer each year. More than 50,000, 52, 53,000 die of pancreatic cancer. That tells you it's pretty deadly. And the main reason is that by the time we find that a person has pancreatic cancer, it's already spread. And patients in whom it's spread, there's no cure for it. And it's pretty rapid. It's pretty widespread by that time. And the chemotherapies, frankly, we have, aren't that effective occasionally. And I actually have a very dear friend, a guy well known to the healthcare community, Leonard Shaffer, who had pancreatic cancer and actually looks like he's been cured of it. But it was found incidentally. They weren't looking for the pancreatic cancer was found incidentally. And let me just tell you, the treatment to cure him was horrendous.
[02:14]
A
So I have heard for as long as, I mean, I can remember that pancreatic cancer was this sort of this. This impossible. Not impossible, but just the most difficult research was going nowhere. It was so hard. Why was it so hard? Why has it been so hard to Attack.
[02:29]
B
It has been deadly. And we used to just sort of shake your head. Another patient with pancreatic cancer, less than 15% of people live for five years. And the chemos just don't work against it. It has this, and this is key to the breakthrough. It has this, what's called the Ras mutation. Ras is a family.
[02:53]
A
Ras, right?
[02:54]
B
Ras, Ras, big R, big A, big S, right? And this is a family of genes that are critical for telling cells when to divide and when to differentiate to become more mature kind of cells. And the big problem in pancreatic cancer is that the Ras mutation is turned on. So it just says divide, divide, divide, divide, divide. And you can't turn it off. And for a long time, you know, this, this sends molecular signal into the cell. And for a long time people refer to this mutation as undruggable. They couldn't find a drug to get in there. And what has happened is that they've found some ways around that problem by targeting it independently. And also they've actually combine multiple approaches to deactivating the Ras gene and the mutated gene. So it's not always on. And it's sort of three different approaches that combine into one pretty amazing response by turning the Ras down and really stopping the cells from proliferating. And it also accumulates in the cell. And that's another very important finding. So one of the. Sorry, John, I'm going on too. John.
[04:23]
A
No, no, no, this is interesting. Keep going.
[04:25]
B
One of the big problems of chemotherapy, as everyone knows, is you get all these side effects. Nausea, vomiting, hair loss, diarrhea, you know, your blood counts go down. That is a response of chemotherapy not targeting the cancer, but targeting all these other normal cells and causing them to die as well. That's the cost we take for the chemotherapy affecting the cancer. One of the interesting things about this new drug is that it actually accumulates in the cancer. And so the, the effect on other cells is way, way less. And it doesn't affect the them and kill normal cells and kill them. And so that's a big additional advantage. So one of the surprising things certainly to a regular oncologist is how few serious side effects there were. It's not like there were no side effects, but they were what we call grade one or two, not grade three or four, much less life threatening. So that means it's very tolerable. So you've got this bad disease with a very tolerable and really much more effective therapy. That's a kind of winning combination. You'd love to get in any oncology setting.
[05:51]
A
And what are the side effects? Because, I mean, I think this is the drug, right, that Ben Sasse is also taking, I think.