Knock Knock, Hi! with the Glaucomfleckens

We're dropping this bonus episode because something genuinely historic happened in oncology and we couldn't wait until our regular schedule to talk about it. Dr. Mark Lewis, GI medical oncologist, pancreatic cancer survivor, and one of our absolute favorite guests. He just got back from ASCO, the Super Bowl of oncology, where a new drug called daraxonrasib received one of only about six standing ovations in the conference's history, including applause that broke out mid-sentence when researchers showed the survival data on-screen. The drug targets a mutation that drives the vast majority of pancreatic cancer and has been considered "undruggable" for decades and it works not by attacking the mutation directly, but by cutting off the downstream signals it sends, like snipping the wire instead of fighting with the switch.

The results are remarkable. In patients who had already received standard chemotherapy, daraxonrasib roughly doubled survival time and delivered it in pill form rather than an IV every two weeks, a meaningful quality-of-life difference for people who are already facing the hardest year of their lives. Mark walks us through the science, the side effects (rash, because RAS proteins live in skin too), the path to FDA approval, and what this means beyond pancreatic cancer, the same KRAS mutations show up in about 30% of lung cancers and 40% of colon cancers.

Takeaways:


Pancreatic cancer has been devastatingly hard to treat, 85% of patients are incurable at diagnosis because it spreads silently and there's no good screening, leaving most patients with a median survival of about a year on IV chemotherapy.


KRAS, the mutation driving nearly all pancreatic cancer, was long considered "undruggable", the protein was so smooth and spherical that no drug could bind to it, and researchers were actively discouraged from pursuing it as a target.

Daraxonrasib works by cutting the power rather than fighting the switch, instead of binding to the KRAS protein itself, it uses molecular glue to interrupt the downstream growth signals the mutation sends, an approach that took decades to develop and wasn't taken seriously until now.


The trial results roughly doubled survival and the treatment is a daily pill, not an IV, patients who had already been treated with chemotherapy gained approximately an additional year of life with improved quality of life, which represents one of the most significant advances in pancreatic cancer treatment in decades.


This breakthrough has implications far beyond the pancreas, KRAS mutations drive about 30% of lung cancers and 40% of colon cancers too, and proving the target is druggable opens the door to a new generation of treatments across multiple cancer types.

Want more Dr. Mark Lewis?

X: @marklewismd

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A friendly reminder from the G’s and Tarsus: If you want to learn more about Demodex Blepharitis, making an appointment with your eye doctor for an eyelid exam can help you know for sure. Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://www.EyelidCheck.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ for more information. 

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I’m back from a whirlwind speaking tour where I realized my entire social media presence might just be a long-con ruse to get a captive audience of 1,000 electrophysiologists to look at my genetic testing report. I officially "locked the doors" at the Heart Rhythm Society in Chicago until someone could tell me if my phospholamban mutation actually means anything. Spoiler alert: I met the guy who literally mapped the gene, and he reassured me it’s a "variant of no significance," which is way more comforting than "uncertain significance". I also had a run-in with a couple at a pool in Florida who were dreading the "entertainment guy" with the weird name, only for me to lean over and put them out of their misery.

The real drama this week, though, is in the courtroom: corporate medicine is on trial in Oregon. I’m breaking down the "dummy LLC" loophole that allows out-of-state corporations to replace local, physician-owned groups with locums who don’t know the community. We dive into the PeaceHealth fiasco in Eugene, where a CEO is currently on administrative leave following whistleblower emails that suggest clinical decisions were being influenced for profit. It’s a messy look at hospital contract shenanigans and why having doctors invested in their own community actually matters for patient safety.

Takeaways:


The "Dummy LLC" legal maneuver corporations use to bypass state laws meant to keep medicine physician-owned.


How I used a 20-foot screen and a captive audience of specialists to get a second opinion on my own genetic mutation.


The "cardiology confident" reassurance I received about my heart from the man who mapped the phospholamban protein.


Why the CEO of a major Oregon hospital is on administrative leave following whistleblower emails about clinical interference.

—

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We want to hear YOUR stories (and medical puns)! Shoot us an email and say hi! knockknockhi@human-content.com

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If you want more information on models I use:

Anatomy Warehouse provides for the best, crafting custom anatomical products, medical simulation kits and presentation models that create a lasting educational impact.  For more information go to Anatomy Warehouse DOT com. Link: https://anatomywarehouse.com/?aff=14 Plus for 15% off use code: Glaucomflecken15

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A friendly reminder from the G’s and Tarsus: If you want to learn more about Demodex Blepharitis, making an appointment with your eye doctor for an eyelid exam can help you know for sure. Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://www.EyelidCheck.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ for more information.

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Victor Wembanyama, the 7'5" alien playing for the Spurs, apparently refuses to look at blue light after 9pm, which allows me to get into my love-hate relationship with blue light glasses, the misinformation campaign that has them treating everything from dry eye to macular degeneration, and the one claim that actually holds up: sleep and circadian rhythm.

Then a great Patreon question drops me into retinopathy of prematurity. What it is, why preemies are vulnerable, and how oxygen, vascularization, and laser treatment all fit together. From there, the bigger problem: 90% of U.S. counties don't have a single pediatric eye specialist. Four states, New Mexico, North Dakota, South Dakota, Vermont, have zero pediatric ophthalmologists. And surprise, this comes right back to private equity, because every Knock Knock Eye episode does.

Takeaways:

Blue light blocking glasses have one evidence-based benefit: improving sleep by helping regulate circadian rhythm. Claims about reducing dry eye, eye strain, or preventing macular degeneration are not supported by the data.

Retinopathy of prematurity is caused by a mismatch between an underdeveloped retina and the oxygen exposure premature infants receive — too much supplemental oxygen damages fragile capillaries and can lead to neovascularization, retinal detachment, and blindness.

90% of U.S. counties have no pediatric eye specialist, and New Mexico, North Dakota, South Dakota, and Vermont have zero pediatric ophthalmologists at all, driven by low reimbursement rates and consolidation that deprioritizes the subspecialty.

Private equity-owned ophthalmology practices aren't expanding into pediatric care because it isn't profitable, kids need Medicaid coverage, not cataracts and LASIK, leaving rural and Medicaid families with the fewest options.

A 2025 JAMA Ophthalmology study on AI screening for ROP found the model was sensitive but not specific, it can flag disease, but it still can't determine which babies actually need laser treatment, so human ophthalmologists remain essential.

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We want to hear YOUR stories (and medical puns)! Shoot us an email and say hi! knockknockhi@human-content.com

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If you want more information on models I use:

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A friendly reminder from the G’s and Tarsus: If you want to learn more about Demodex Blepharitis, making an appointment with your eye doctor for an eyelid exam can help you know for sure. Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://www.EyelidCheck.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ for more information. 

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I’m stepping away from the slit lamp this week to talk about a different kind of eye emergency. The ones happening on the front lines of protests across the country. I’ve been seeing way too many videos of people losing their vision to "non-lethal" force, so I invited Adam Rose, the Deputy Director of Advocacy for the Freedom of the Press Foundation, to help us navigate this. Adam has 20 years of journalism under his belt and spends his time making sure the people documenting history don't end up as patients in my clinic.

Whether you’re a journalist, a protester, or just a citizen with a smartphone, this episode is a crash course in exercising your First Amendment rights without losing an eyeball.

Takeaways:


Why a build-up of food gases in an old Thermos can pop a lid with enough force to cause a "ruptured globe" injury.


The difference between a "Democratic physician-owned group" and a "Contract Management Group" staffing your local hospital.


How a doctor living in Illinois can technically "own" an emergency practice in Oregon through a legal loophole.


Why Will thinks "home call" in residency is just a clever way to skirt work-hour restrictions.


The "Glock Flecking Fodder Ability Scale" for determining which medical specialties are the easiest to make fun of.

—

To Get Tickets to Wife & Death: You can visit Glaucomflecken.com/live 

We want to hear YOUR stories (and medical puns)! Shoot us an email and say hi! knockknockhi@human-content.com

Can’t get enough of us? Shucks. You can support the show on Patreon for early episode access, exclusive bonus shows, livestream hangouts, and much more! –⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ http://www.patreon.com/glaucomflecken⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ 

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If you want more information on models I use:

Anatomy Warehouse provides for the best, crafting custom anatomical products, medical simulation kits and presentation models that create a lasting educational impact.  For more information go to Anatomy Warehouse DOT com. Link: https://anatomywarehouse.com?aff=14 Plus for 15% off use code: Glaucomflecken15

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A friendly reminder from the G’s and Tarsus: If you want to learn more about Demodex Blepharitis, making an appointment with your eye doctor for an eyelid exam can help you know for sure. Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://www.EyelidCheck.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ for more information.

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I'm not in a great mood and I'll tell you why. A mini fridge in our family room sprang a slow leak, and before I knew it I was $5,000 deep in a restoration black box with no idea whether any of those numbers were real. Which, of course, got me thinking about healthcare cost transparency, because everything eventually does.

From there I get into Oregon's SB 951, the strongest corporate practice of medicine law in the country, and what it might mean in 2029 for the private equity firms (and one suspiciously friendly-sounding Canadian pension fund) currently buying up ophthalmology.

After the break I cross over into veterinary land to talk about the cow eye dissection I ran with about 50 middle schoolers at my kids' school. The tapetum lucidum, the onion-layered lens, why goats have rectangle pupils, and the brand-new respect I now have for teachers. We finish up in the animal vision spectrum, where the mantis shrimp absolutely embarrasses the rest of us.

Takeaways:

Oregon's SB 951 requires all medical practices in the state to be physician-owned and free of outside investor influence by 2029, a potential turning point for private equity in ophthalmology

NVISION Eye Centers is majority-owned by Ontario Teachers' Pension Plan Board, a $250 billion Canadian fund that functions, in effect, like a private equity firm

The Central Africa Ebola outbreak is unlikely to become a pandemic, but reduced WHO funding after the U.S. withdrawal weakens global surveillance and rapid response

The tapetum lucidum is a reflective layer behind the retina in cows, dogs, cats, and many other mammals that bounces light back through the photoreceptors, dramatically improving night vision and explains the glowing-eyes phenomenon

Humans have three color cones; mantis shrimp have 12 to 16 plus UV, infrared, and polarized light detection; dogs and cats see dichromatic blues and yellows; whales and dolphins see only in monochrome

To Get Tickets to Wife & Death: You can visit Glaucomflecken.com/live 

We want to hear YOUR stories (and medical puns)! Shoot us an email and say hi! knockknockhi@human-content.com

Can’t get enough of us? Shucks. You can support the show on Patreon for early episode access, exclusive bonus shows, livestream hangouts, and much more! –⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ http://www.patreon.com/glaucomflecken⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ 

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If you want more information on models I use:

Anatomy Warehouse provides for the best, crafting custom anatomical products, medical simulation kits and presentation models that create a lasting educational impact.  For more information go to Anatomy Warehouse DOT com. Link: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://anatomywarehouse.com/?aff=14⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Plus for 15% off use code: Glaucomflecken15

--

A friendly reminder from the G’s and Tarsus: If you want to learn more about Demodex Blepharitis, making an appointment with your eye doctor for an eyelid exam can help you know for sure. Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://www.EyelidCheck.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ for more information. 

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