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
North America Stories
15/07/2026
The 2026 FIFA World Cup is a big deal for DAZN, which has distribution rights in three markets: Italy, Spain, and Japan. Each requires a different editorial app...
15/07/2026
As sports-media organizations manage rapidly growing content libraries and incre...
15/07/2026
HBS director of digital Johannes Franken talks SVG Europe through the operation built to serve FIFA World Cup 2026 rights holders remotely from Stratford, east ...
15/07/2026
IBC has unveiled the conference program for IBC2026, with this year's event ...
15/07/2026
Software-defined wideband RF platform supports 96-kHz monitoring, streamlined fr...
15/07/2026
New AI-powered module enables broadcasters and content owners to extract dialogu...
15/07/2026
Weeklong gathering at EBU headquarters will test new IPMX capabilities and expand certified product ecosystem...
15/07/2026
Force Tech has announced the appointment of Bryan Adams, CTS, as Vice President of Integration. Adams will oversee AV and broadcast integration project delivery...
15/07/2026
USA Sports has announced an exclusive English-language agreement with the Bundes...
15/07/2026
ITV Sport's FIFA World Cup 2026 coverage has been produced from one of the m...
15/07/2026
Program will provide professional camera kits, training, and technical support to participating local newsrooms...
15/07/2026
San Francisco church becomes first U.S. deployment of the 2 M/E production switcher...
15/07/2026
Former ESPN and NFL Network executive to advise startup league on media, distribution, technology, and fan engagement...
15/07/2026
The Houston-based RSN is the live-game home of the Astros and Rockets...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
GigaCloud, a leading Ukrainian cloud service provider, and Cubbit, the first geo-distributed cloud storage enabler, today announced a new Business Alliance Part...
15/07/2026
SMPTE, the global society for media professionals, technologists, and engineers, has announced the launch of the SMPTE 110th Anniversary Campaign, a fundraising...
15/07/2026
Studio Technologies, a leading manufacturer of high-quality audio, video, and fiber-optic solutions, unveils the new StudioComm Model 762 Stereo Level Control, ...
15/07/2026
COW Jobs: Producer, Virtual Events - Hybrid, Full Time, Salaried
Brie Clayton July 15, 2026
0 Comments
Producer, Virtual Events (Hybrid | Full-time | ...
15/07/2026
Brazilian media organization builds nationwide CDN with Broadpeak's high-performance software for low-latency streaming and new content distribution service...
15/07/2026
DHD announces a new utility designed to increase the efficiency of its audio mixing systems during initial installation and subsequent configuration.
Anyone w...
15/07/2026
BCNEXXT Brings Next-Generation Vipe to IBC2026, Breaking the 1:1 Channel-to-Server Ratio New innovations liberate broadcasters from legacy playout infrastructur...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Home to leading manufacturers, robotics pioneers, infrastructure builders and gaming, of course, Japan is one of the world's centers of AI - building across...
14/07/2026
South end zone videoboard, cloud-based control system will be ready for 2026 football season...
14/07/2026
Redesigned website, enhanced mobile app unify content, ticketing, and personalized fan engagement...
14/07/2026
Agreement spans sponsorship sales, digital monetization, radio production, and new practice facility naming rights...
14/07/2026
Independent league adds 14 regional sports network affiliates, growing distribut...
14/07/2026
New strategy aims to unify competitions, content, fan engagement, and commercial...
14/07/2026
ESPN and Disney+ become exclusive home of PFL events in key international MMA market...
14/07/2026
Gill will oversee engineering, technology, and sports operations across the company's 64 local television stations...
14/07/2026
Submitted by North American Broadcasters Association (NABA)
As broadcasters con...
14/07/2026
Modernized mobile unit combines HOME Apps, mc 56 console, and IP infrastructure ...
14/07/2026
Every match of the 32-team tournament will air across ION and Scripps Sports platforms in English and Spanish...
14/07/2026
FloHockey to stream every game of the annual international tournament under four...
14/07/2026
Victory+ telecasts to be simulcast on TEGNA-owned station, expanding free local distribution...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
IBC2026 has unveiled a powerful Conference programme bringing together global media leaders, technology innovators, creators, sports organisations, broadcasters...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Broadcast Solutions, a leading systems integrator and provider of innovative solutions for the broadcast media industry, has delivered two highly capable outsid...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Telos Alliance Adds AudioShake Source Separation to Minnetonka Audio AudioToo...
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.
