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Unraveled is a podcast produced by Dana-Farber that explores the mysteries of the science of cancer. Veteran broadcaster Ken Shulman digs into the cutting-edge science that is transforming cancer research and providing hope for scientists and cancer patients.
In Season 2, we explore the theme of momentum. The momentum that takes therapies from test bench to bedside, and then back to test bench for fine-tuning. The momentum provided by researchers, who defy headwinds and even gravity to keep science moving forward. And the momentum that doctors harness, with medicines and care that can transform once lethal cancers into treatable conditions. Listen to the trailer below.
Season 2 Trailer
Season 2, Episode 1: BCL-2 Inhibitors: Driving Cells to Destruction
The story begins decades ago with a man named Stanley Korsmeyer, who led the molecular oncology program at Dana-Farber from 1998 until his death in 2005. He discovered that B cell cancers like CLL over-produced a protein called Bcl-2, and interfered with apoptosis, or programmed cell death. But how that went from an interesting discovery to a game-changing cancer drug is a story of persistence and momentum, and it's the first episode of season two of Unraveled.
Season 2, Episode 2: Thalidomide and its Second Act in Multiple Myeloma
Momentum isn't always one way. And it's not always constant. Sometimes it shoves you sideways, sometimes it stops you in your tracks. And sometimes only sometimes, it drives you to write one of the most astonishing second acts in all of medicine. That's the story of thalidomide, its second act in multiple myeloma, and the promise of protein degradation.
Season 2, Episode 3: Stop the Division: CDK-4/6 Inhibitors and the Cell Cycle
Cancer is often a problem of cell division; cancer cells keep doubling and doubling, faster and faster. Eventually, they crowd out the healthy cells we need to survive. So researchers proposed a question: Why not stop that land grab? Why not find a way to jam the gears of the cell cycle to stop cancer cells from dividing? Today, we have drugs that do just that: They're called CDK-4/6 inhibitors. The story of those drugs, the momentum that brought them from bench to bedside, was written largely at Dana-Farber Cancer Institute — and keeps being written today. It's the story we're telling in episode three of Unraveled.
Season 2, Episode 4: Making it Personal: Targeted Cancer Therapies
By the early 2000s, researchers at Dana-Farber and elsewhere knew that a certain protein appeared in many tumors taken from lung cancer patients. Based on that data, doctors started treating those patients with a drug that inhibited that protein. Unfortunately, for reasons that weren't clear at the time, most of the patients didn't respond — but there was a small percentage of patients, about one out of ten, who did. People called it a "Lazarus-like effect."
So how can doctors know which of their patients is Lazarus? How can they know which ones will respond to a drug and which ones won't? In other words, how can they interpret data so it makes sense? That's the subject of this episode of Unraveled about precision medicine and the EGFR discovery. It's an episode that begins with a riddle and ends with a roadmap.
Season 2, Episode 5: With a Little Help From My Friends: Combination Immunotherapy
If there is such a thing as a holy grail in cancer research, a secret spell or golden ring that can ward off any and all forms of the disease, it probably lives somewhere in the realm of immunotherapy. A new category of immunotherapy drugs, called checkpoint inhibitors, take the brakes off the immune system and let the T cells do their job: attack cancer. They've been approved for more than 25 different types of cancer.
However, the average response rate for checkpoint inhibitors is 20 to 30%, which means that it's not working for 70% of the people who take it. So that's the project now: to extend the benefits of immunotherapy to all cancer patients, instead of to just a few. And the best way to do that, it seems, is by doubling down, by pairing immunotherapy with other therapies so patients can benefit from both. It's called combination immunotherapy, and it's what this episode of Unraveled is about.
Season 2, Episode 6: Big Data, AI, and Cancer Research
As our universe of knowledge expands, sometimes incrementally and more often, exponentially, its new dimensions create new challenges. The more we know, the better our tools are, the more choices we have. And that's great, but it's hard to distill mountains of patient data, clinical trials, therapies, discoveries, and a boatload of externalities. Hard to distill all of these into the best possible research and care. Oh, and don't forget the human genome in its almost infinite complexity.
It can be overwhelming when you try to think about it absent, sort of having some help. But what kind of human mind could provide that help? Could it be that the help we need, the intelligence we need isn't human at all.
In this episode, we look at how artificial intelligence (AI) experts, physicians, and ethicists are working together to apply AI to cancer research.
Season 1 Trailer
Season 1, Episode 1: The Wolf in Sheep's Clothing
The parable of the wolf in sheep's clothing reminds us that things aren't always as they seem: bad guys can dress up as good guys to do their bad guy things. There's a wolf in sheep's clothing story in cancer research, complete with a crafty predator, a clever disguise, and a visionary team of researchers who found a way to nab the wolf.
Season 1, Episode 2: Behind the Science of the 2019 Nobel Prize
It's hard to overstate how important oxygen is to life on earth. Almost every living thing on the planet needs oxygen to convert fuel into energy. We can't survive without it, not even for a handful of minutes. Fortunately, our bodies know this, and have developed several rapid response systems to keep us going when oxygen runs low.
A few cancers have found a bug in the system: a way to sound a false alarm and make the body think it's low on oxygen when it's not. These cancers hijack the body's response to feed hungry tumors. It's a complicated and fascinating process, and it earned one Dana-Farber doctor the biggest prize of all.
Editor's note: A few months after the release of this episode, David Livingston, MD, died at the age of 80. He was a mentor to many and a giant in the field of cancer research. Read more about his life and work.
Season 1, Episode 3: A Culture of Mentorship
What do cancer researchers and 15th century Florentine masters have in common? For one, a culture of mentorship. Both come of age in a culture where knowledge is transmitted from master to pupil. In this episode, we take a closer look at that culture and the crucial role mentorship plays at Dana-Farber, with Nobel laureate Dr. William Kaelin.
Season 1, Episode 4: The Blueprints of Your Cells
There are approximately 20,000 genes in the human genome. 20,000 packets that house the blueprints for every human cell. And every cell contains a complete copy of that genome. It's an incredible feat of bioengineering. But here's the question: If every human cell contains every single human gene, how does the cell know what to do? What process determines whether the cell becomes a pancreas or a patella? And what happens if that process falters - if the right gene is selected but is cast in the wrong role?
Season 1, Episode 5: Turning Science Fiction into Fact
It's always fun to think about the future. Flying cars. Cities in the clouds. Colonies on Venus and Mars. OK, we didn't end up living like the Jetsons. But a few of those visions did come true. And Judy Wilkins knows that first-hand. Wilkins is a former patient at Dana-Farber and is the poster child for a bold new therapy where science fiction becomes science fact.
Season 1, Episode 6: Dana-Farber in the Time of COVID
A beauty… that in some cases becomes tragic. It's not the way most people would describe a virus. In the simplest of terms, a virus is a snippet of genetic code. It can't reproduce on its own. In order to replicate, it needs to infect and hijack a living cell.
Scientists can't even agree on whether viruses are alive or dead. What they do know is that every so often, one of them goes, well, viral. And when it does, it can bring everything to a skidding halt.
Well, almost everything. One thing the COVID-19 pandemic didn't stop was cancer. And that meant that everyone at Dana-Farber had to find a way to keep on working and find a way to keep themselves and their patients safe.
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