Andrew Waters

Excited to share my first last-author research paper in @CR_AACR where we comprehensively identify and validate resistance mechanisms to KRAS inhibitors in #PancreaticCancer. This work was led by a fantastic medical resident @SzuAunLongMD, and two phenomenal grad students Haley Todd and @grace_goodhart. @SyedAAhmad5 @ambermamparo @bryant_kl @G_AaronHobbs @UCincySurg @Julien__Dilly @cjder23 Take-home messages: 1. KRAS Q61H-mutant PDAC is genetically and pharmacologically less dependent on KRAS for survival. We think this is due to biochemical idiosyncrasies that create an increased dependence on WT RAS isoforms. This creates a susceptibility to combined EGFR inhibition in a KRAS Q61H-mutant setting in PDAC models. 2. Additional validated hits include PI3K alpha and gamma, YAP, CK2 (formerly known as casein kinase 2). 3. We also generated KRASi-resistant PDAC cell lines that underwent an EMT, had low ERK MAPK signaling (yet remained dependent on ERK MAPK signaling), and we determine that after a 30 day compound removal, resistance was largely reversible. Support from @theNCI @AmericanCancer @PanCAN among others. aacrjournals.org/cancerres/arti…

@Aiims1742 I saw that too!

Well if that isn’t the perfect encapsulation of #AACR26

What a time to be alive when I have to choose between attending Brian Wolpin’s talk on Daraxonrasib + chemo in 1st line #PancreaticCancer OR @RevMedicines talk on their preclinical asset RM-055 that overcomes KRAS inhibitor resistance, BOTH at the exact same time! #AACR26

If KRAS biology ever wins the Noble prize. These Godfathers of RAS should be on the list!#AACR26 @kevansf @frankpmccormick @cjder23 @RevMedicines @KRASKickers

Zoldonrasib Deemed Safe, Effective in KRAS G12D-mutant #LungCancer aacrjournals.org/cancerdiscover… #AACR26 @CD_AACR

This is perhaps my most rewarding grant! @Run4Purple stepping up to support our research ideas and the PhD students in the lab! Training the next generation of pancreatic cancer researchers while moving the needle!

@DelgiornoKathy @Run4Purple Thanks @DelgiornoKathy! Are you at AACR? (I arrive tomorrow night)

@Run4Purple Congrats @AndrewMWaters !!

We are excited to announce that we have invested $375,000 at the University of Cincinnati through our Research Recovery Grant! To read more about this research study, click the link: bit.ly/3OuUis8

🚨🚨🚨 RASOLUTE-302 Ph3 is POSITIVE "Daraxonrasib demonstrated a median OS of 13.2 months versus 6.7 months for chemotherapy, with a hazard ratio of 0.40 (p < 0.0001)".... WOW! AMAZING news for patients with #PancreaticCancer The RAS Revolution is ON!! ir.revmed.com/news-releases/…

I'm not, and I agree with you.I'm an NIH-funded KRAS researcher. But the concept and methods for generating Daraxonrasib were purely a company endeavor. My major point here is that these drugs have lots more promise than Jason indicates. Daraxonrasib extends life (15.7 months) in a heavily pretreated population more than most pdac patients' entire disease journey from diagnosis to death (11.1 months).

@AndrewMWaters @LocasaleLab NIH typically doesn't fund that much of drug development - don't discount the decades of NIH funded research into making RAS druggable that laid the foundation for emerging drugs today.

I listened to the podcast from Ben Sasse. It’s poignant, gut-wrenching, and a must-listen for anyone practicing oncology or doing cancer research. Ben Sasse was diagnosed with late stage pancreatic ductal adenocarcinoma (PDAC), the most lethal form of cancer and given a few months to live. He speaks candidly about that experience and reflects on other important parts of his life. Some do get cured of cancer. Jimmy Carter who had what was thought to be a terminal cancer is a well-known example—he had a complete response to an immune therapy. Those drugs can be curative, but overall they work in a very small fraction of patients, on the order of a few percent. Ben Sasse has stage IV PDAC. It’s usually detected at a point where surgery is not possible, and chemotherapy and radiation offer limited benefit. It’s also one where the immune therapies don’t work. He is taking a KRAS-targeted drug, designed to act on the key mutation in the cancer. These were long viewed in oncology as the major breakthrough, but the reality is they often produce dramatic initial responses followed shortly by resistance, typically translating into 6–12 months of additional life. We’ve spent decades and enormous NIH/NCI resources studying what has led to the culmination of this new drug. The net impact on oncology practice has been very modest. Meanwhile, early detection and prevention—where the potential impact is far greater—remain comparatively neglected. Spontaneous remission and other forms of remarkable recovery are real and occur in a small percentage of patients. It is still a possibility. They’re rarely emphasized in research or practice because oncologists and medical practitioners are trained to speak in absolute terms.

Mark Cuban just saved baby Stella’s life. Stella was diagnosed with aggressive cancer at just four months old. Her mother posted a TikTok video showing her speaking with the insurance company, which was denying a medical lift that could have saved Stella’s life. The lift would have transported her from Minneapolis, Minnesota, to Cincinnati Children’s Hospital in Ohio for a T-cell transfusion that is only available at that facility. The insurance company claimed Stella was well enough to travel by road—even though both her parents and doctors said she was not. In fact, doctors refused to discharge her from the hospital due to her failing liver. Her mother posted the video begging for help—either a private plane or assistance securing a medical lift. The video caught the attention of billionaire Mark Cuban, who immediately stepped in and funded the entire transport, along with everything needed to get Stella to Cincinnati. Stella was scheduled for her T-cell transfusion two days ago. As soon as I have an update, I will provide one. And no, you do not hate insurance companies enough.

@AntjeSchaeferZ @AmericanCancer @MCWCancerCenter @McwPharmTox 💪🏻

Inspiring meeting with over 80 community health workers, talking about my #gastricCancer research & providing information & resources to improve early detection + patient outcomes. Thanks @AmericanCancer @MCWCancerCenter! #cancerResearch @McwPharmTox

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Super proud of this grant! In tough times, @Run4Purple came to the rescue. I am running the @RunFlyingPig half-marathon to fundraise for the #pancreaticcancer foundation that chose to invest in our research ideas! Join me and/or donate 👇 charity.pledgeit.org/f/yhy6m1jw51

What an honor to share the exciting work our lab is doing at @uofcincycancer with the other "RASophiles" at @AACR #AACRras26. And what an awesome opportunity to share the stage with the legends of the field.

@AACR #AACRras26 was a fantastic opportunity to hear about the latest science, discuss our own science, and build collaborations!

What an amazing 3.5 days discussing all things RAS! Thanks to the AACR staff and all their hard work and my coorganizers ! @AACR #AACRras26

Dieter Saur, Zachary Hauseman, James Duncan, and Jennifer Klomp discussed "Effector Signaling" in a plenary session at the AACR Special Conference on RAS Oncogenesis and Therapeutics. #AACRras26 @SaurLab @ZHauseman

The AACR Special Conference on RAS Oncogenesis and Therapeutics opens today in Los Angeles with a keynote address by Channing Der. #AACRras26

Drugging RAS: What a Long, Strange Trip It’s Been— Channing Der addressed this topic in a keynote address to open the AACR Special Conference on RAS Oncogenesis and Therapeutics. #AACRras26