Structural studies offer how-to guide for designing cancer drugs By revealing how the structure of the PI3K protein changes in cancer cells, Scripps Research scientists point toward ways to target it with drugs.
December 08, 2022
LA JOLLA, CA To design drugs that stall the growth of aggressive cancers, it helps to know the structures of the proteins that are revving the cancers' engines.
In a series of three papers published in Proceedings of the National Academy of Sciences, Scripps Research scientists have illuminated the three-dimensional structure of phosphoinositide 3-kinase alpha (PI3K ), a protein often mutated in cancer cells. Moreover, the research team shed light on how that structure changes with the cancer-associated mutations, paving the way for drugs that could target only the mutated versions.
We hope that these detailed structural findings lead to the discovery of drugs that affect cancer cells but not healthy cells, says senior author Peter Vogt, PhD, a professor in the Department of Molecular Medicine at Scripps Research. That could potentially eliminate the side effects associated with current PI3K drugs.
PI3K plays a central role in cell survival and growth. In healthy cells, the protein is flipped on and off as needed. But in numerous types of cancer including breast, colorectal, endometrial and brain mutations in PI3K make it active all the time, encouraging the unchecked growth of the tumors. Current drugs that aim to put the brakes on PI3K bind to a section of the protein that rarely changes between healthy and mutated versions; this means all the PI3K in the body is shut off. Because of that, these PI3K inhibitors carry a long list of side effects and toxicities.
To solve this problem, you have to make inhibitors that only recognize the mutated versions of PI3K , says Vogt. But to do that, you need structural information about what differentiates mutated, overactive PI3K from normal PI3K .
This is no easy feat: PI3K is a particularly flexible, wiggly protein, so it's difficult to get a single snapshot of its structure. Vogt's group, however, discovered that when PI3K was bound to one of the existing inhibitors, it became more stable. In PNAS papers published in November 2021 and September 2022, they used a type of imaging technique known as cryogenic electron microscopy (cryo-EM) to work out the three-dimensional structure of PI3K . With this knowledge, they first examined the structure of PI3K attached to the inhibitor. Then, to visualize the protein without the inhibitor, they used cross-linking molecules to attach different parts of PI3K to itself, stabilizing the most flexible parts of the protein.
More recently, the research team used the same cryo-EM toolbox to piece together the structure of two mutated versions of PI3K often found in cancer cells. That work, published last month in PNAS, showed how some segments of the mutated PI3K resemble the activated form of PI3K .
There are quite dramatic structural changes, says Vogt. And in the end, the changes essentially mimic the normal activated form of the protein, with the only difference being that it's always in this active structure.
The findings point toward ways to use drugs to shut off this always-on version of PI3K in cancer cells, without turning off healthy PI3K . The key, Vogt says, is that the drugs will need to bind to a different part of the PI3K protein than where the existing PI3K inhibitors bind a part that varies structurally between the healthy and mutated versions of the protein.
His lab group is following-up on this research with additional studies revealing how current drugs change the structure of PI3K .
In addition to Vogt, authors of the studies, Cryo-EM structures of PI3K reveal conformational changes during inhibition and activation, Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K , and Cryo-EM structures of cancer-specific helical and kinase domain mutations of PI3K , include Su Yang, Jonathan R. Hart, Lynn Ueno and Alexandra Quezada of Scripps Research.
The work at Scripps Research was supported by funding from the National Cancer Institute (R35 CA197582 and R50 CA243899).
Cancer Molecular and Cellular Biology Vogt, Peter
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
02/05/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
01/05/2026
January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...
06/04/2026
Michigan legends bring a new voice to the broadcast as TNT Sports and CBS Sports...
06/04/2026
From high school sports all the way up to the major leagues, building high-quali...
06/04/2026
Quickplay, an AI company for the media and entertainment industry, has been accepted into the Advanced tier of the TwelveLabs Ecosystem Partner Program. Quickpl...
06/04/2026
Grass Valley has announced the Future Playmakers Program, a global initiative to...
06/04/2026
El l der de operaciones impulsa la producci n en estudio mientras encuentra insp...
06/04/2026
The ops leader helps lead the charge in studio for the Spanish-language broadcas...
06/04/2026
Behind The Mic provides a roundup of recent news regarding on-air talent, includ...
06/04/2026
The National Hockey League (NHL), in partnership with Verizon and the New Jersey Devils, today announced the opening of the NHL Innovation Lab powered by Verizo...
06/04/2026
Rock League, a new professional curling league, has announced that ESPN+ will stream its inaugural 2026 season for fans in the United States. The first Rock Lea...
06/04/2026
Advanced Systems Group has announced the appointment of Andrea (Andy) Cummis as Vice President of Systems Design and Engineering. In this role, she will lead de...
06/04/2026
Backed by Bolt Ventures, the venture brings Bryson DeChambeau, Grant Horvat, and...
06/04/2026
With this environment we can start that collaboration even earlier because we ca...
06/04/2026
Like the immortal lives of vampires, some stories never really end. That's t...
06/04/2026
As podcasting continues to evolve, growth increasingly means building beyond aud...
06/04/2026
Multiband dynamics plug-in enhanced
California-based developer FSK Audio have released a significant update for their innovative multiband dynamics processo...
06/04/2026
Share official & user-created full-rig presets
IK Multimedia's latest TONEX update makes it possible for users of the popular amp and effects modelling ...
06/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/04/2026
Dalet Showcases Dalia Agentic AI and End-to-End Media Workflows at NAB Show 2026
Brie Clayton April 6, 2026
0 Comments
Dalet, a leading technology and...
06/04/2026
OpenDrives Shows Off Sports Expertise in Sports Business Hub located in NAB Show...
06/04/2026
Proton to Demonstrate 3D Application at NAB 2026
Brie Clayton April 6, 2026
0 Comments
Yet further creative potential unleashed through innovation in ...
06/04/2026
Autoscript Highlights Voice-Driven Prompting and PTZ Solutions at NAB 2026
Brie Clayton April 6, 2026
0 Comments
Experience Autoscript Voice, PTZ prom...
06/04/2026
Mediaproxy Highlights Significant Enhancements to its LogServer suite at NAB Sho...
06/04/2026
Wayne, N.J., April 6th, 2026 Phantom High-Speed announces the release of PCC 4...
06/04/2026
April 6th, 2026
TRIBECA STUDIOS AND LILLY ANNOUNCE WINNERS OF INAUGURAL VITAL...
06/04/2026
Back to All News
Netflix Expands Kids Entertainment Lineup With Playground App ...
05/04/2026
Tackles all reported bugs!
SoundBridge have just announced the launch of a new update that introduces a couple of minor changes to their remote collaboratio...
04/04/2026
The University of Arizona's Men's Basketball team has only loss twice th...
04/04/2026
1080p HDR arrives, a new generation of storytelling tools takes center stage, an...
04/04/2026
Michigan legends bring a new voice to the broadcast as TNT Sports and CBS Sports...
04/04/2026
Faster, cleaner and more intuitive than ever
The control software for Flock Audio's digitally controlled patchbay systems has just been treated to an up...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/04/2026
DHD Introduces AI-Based Audio Noise Reduction to XD3 IP Core
Brie Clayton April 3, 2026
0 Comments
The accompanying image shows the rear panel of the ...
04/04/2026
Macnica Redefines ST 2110 Flexibility with Two Speeds on One Card
Brie Clayton April 3, 2026
0 Comments
New for NAB Show 2026, MEP100 SmartNIC now sup...
04/04/2026
Unified Media Workflows for Story-Centric Production
Brie Clayton April 3, 2026
0 Comments
Framelight X unifies field capture, editing and publishing ...
03/04/2026
Michigan's Fab Five will reunite for an alternate presentation of the Mich...
03/04/2026
Avid will exhibit at NAB Show 2026 (April 18-22, Booth N2226, Las Vegas Convention Center), demonstrating its Content Core platform and new AI-driven workflow c...
03/04/2026
Mark Roberts Motion Control (MRMC) has announced the appointment of Nick Barthee as Chief Operating Officer.
The announcement follows MRMC's transition fro...
03/04/2026
Interra Systems has announced that Elite Media Technologies has selected its BATON file-based QC solution for media workflows. Elite Media Technologies speciali...
03/04/2026
Ateme has announced that Moldtelecom has deployed Ateme technologies across its streaming workflow, covering encoding, delivery, operations, and analytics.
Mol...
03/04/2026
Grass Valley will demonstrate Framelight X, its content management platform, at NAB Show 2026. The platform connects capture, ingest, editing, and publishing in...
03/04/2026
Encompass Digital Media and Techex have announced a cloud-native Master Control ...
Structural studies offer how-to guide for designing cancer drugs By revealing how the structure of the PI3K protein changes in cancer cells, Scripps Research scientists point toward ways to target it with drugs.
