Sony Pixel Power calrec Sony

December 08, 2022

09/12/2022

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
LINK: https://www.scripps.edu/news-and-events/press-room/2022/20221208-vogt-...
See more stories from scripps

Most recent headlines

06/10/2025

France Tlvisions Wins Prestigious 2025 EBU Technology & Innovation Award in Groundbreaking Collaboration with Dalet

France T l visions, France's leading broadcaster, has received the 2025 EBU ...

04/09/2025

Monumental Sports & Entertainment and Dalet Win Prestigious 2025 NAB Show Project of the Year Award

Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...

07/08/2025

Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, Redefining In-Car Entertainment Experience

July 8 2025, 22:30 (PDT) Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, R...

11/07/2025

2025 Sundance Institute Producers Lab Fellows Announced

PARK CITY, UTAH, July 11, 2025 - The nonprofit Sundance Institute announced today the 11 producers chosen for its annual Producers Labs, returning to Ucross Fou...

11/07/2025

Superman' Filmmaker James Gunn Reveals the Playlists Inspired by Your Favorite Characters

If you've ever wondered what might be playing in Clark Kent's headphones...

11/07/2025

L3Harris Delivers First P-8A Poseidon Aircraft to US Navy

L3Harris Technologies President of Intelligence, Surveillance and Reconnaissance Jason Lambert and General Manager of L3Harris Waco facility Sean Ling held a ce...

11/07/2025

WETA Launches WETA+ Free Streaming Service

ARLINGTON, Va. WETA, the flagship public media station in the national capital area, has launched WETA+, a new streaming service tailored for the local Washingt...

11/07/2025

TV Tech's Top Regulatory Stories of 2025

The Federal Communications Commission has emerged as one of the central players in the broadcast TV landscape in 2025, with its deregulatory policies sparking h...

11/07/2025

Calrec to Feature Suite of Interconnected Audio Solutions at IBC2025

Calrec will introduce usability, customization and system enhancements across its entire range of Argo consoles during IBC2025, Sept. 12-15, at the RAI Amsterda...

11/07/2025

Encompass Supports DAZN's Coverage of 2025 FIFA Club World Cup

LONDON Encompass Digital Media said it will support live and on-demand viewing of the 2025 FIFA Club World Cup across multiple global regions for sports enterta...

11/07/2025

SBE Survey: Certified Broadcast Engineers Earn More

Two-thirds of broadcast engineers reaped the benefits of a pay raise within the last year....

11/07/2025

SmallHD Unveils Quantum 27 OLED Monitor

CARY, N.C. SmallHD has launched the Quantum 27, a new 26.5-inch Quantum-Dot OLED monitor designed to deliver postproduction image quality in a compact, set-frie...

11/07/2025

Tegna Will Pay $225K to Settle FCC Investigation

The Federal Communications Commission's Enforcement Bureau and Tegna have entered into a consent decree that will settle an investigation into the accidenta...

11/07/2025

Sens. Markey, Lujn Again Call for FCC Vote on Paramount-Skydance Merger

WASHINGTON Following news in early July that Paramount had settled President Donald Trump's lawsuit, Sens. Edward J. Markey (D-Mass.) and Ben Ray Luj n (D-N...

11/07/2025

Model/Actriz Performs Lead Single Cinderella on The Late Show with Stephen Colbert

Model/Actriz Performs Lead Single Cinderella on The Late Show with Stephen Colbe...

11/07/2025

Behind the Mic: Amazon Prime Preps for First Season of NBA Action; MSG Networks Adjusts Broadcast Booths for Rangers, Devils

Behind the Mic: Amazon Prime Preps for First Season of NBA Action; MSG Networks ...

11/07/2025

SVG New Sponsor Spotlight: Suite Studios' Craig Hering on Adapting to Clients' Needs With Scalable Cloud-Based Storage

SVG New Sponsor Spotlight: Suite Studios' Craig Hering on Adapting to Client...

11/07/2025

2025 SVG Content Management Forum Breaks Down AI's Impact, Continued Transition to the Cloud

2025 SVG Content Management Forum Breaks Down AI's Impact, Continued Transit...

11/07/2025

A Journey HOME: University of Nebraska's HuskerVision Goes IP

A Journey HOME: University of Nebraska's HuskerVision Goes IP Leaders from the HuskerVision and Lawo share their IP learnings By SVG Staff Friday, July 1...

11/07/2025

CMSI, Remote Picture Labs, Ace ESPN's Cloud-Based Editing Efforts for Wimbledon

CMSI, Remote Picture Labs, Ace ESPN's Cloud-Based Editing Efforts for Wimble...

11/07/2025

Netflix Enters the Live-Boxing-Production Ring for Round 2 With Historic Taylor-Serrano 3 Card at MSG

Netflix Enters the Live-Boxing-Production Ring for Round 2 With Historic Taylor-...

11/07/2025

'Too Hot to Handle: Italy' Is Coming on July 18 Only on Netflix

Back to All News Too Hot to Handle: Italy Is Coming on July 18 Only on Netflix Entertainment 11 July 2025 GlobalItaly Link copied to clipboard July 11, 20...

11/07/2025

Netflix Will Release 'Death Inc.' Seasons 1, 2 and 3

Back to All News Netflix Will Release Death Inc. Seasons 1, 2 and 3 Entertainment 11 July 2025 GlobalSpain Link copied to clipboard Season 1 Season 2 Se...

11/07/2025

AI and Multimedia Authenticity Standards Collaboration

AI and Multimedia Authenticity Standards Collaboration launches two papers to guide the future of AI integration, today at the AI for Good Global Summit The...

11/07/2025

A Gaming GPU Helps Crack the Code on a Thousand-Year Cultural Conversation

Ceramics - the humble mix of earth, fire and artistry - have been part of a global conversation for millennia. From Tang Dynasty trade routes to Renaissance pa...

10/07/2025

Taliban repression silences award-winning Afghan woman journalist

The current holder of the prestigious Thomson Foundation Young Journalist of the Year Award has been forced to stop reporting over fears for her safety in Afgha...

10/07/2025

A New Report Puts Aussie Artists in the Spotlight

Spotify is turning up the volume on Australian music with a multipronged initiative designed to highlight the dominance of Australian artists on the global stag...

10/07/2025

Spotify Toasts Oasis's Return With Exclusive Ways for Fans to Get Closer to the Music That Defined a Generation

This is not a drill: Oasis is back on the road-marking its first live performanc...

10/07/2025

Spotify and Youth Music Open Doors for Future Artists

The music industry depends on fresh ideas, bold voices, and emerging talent. Yet across the U.K., too many young musicians lack the space to develop their craft...

10/07/2025

Nielsen Appoints Richard Pacheco as Head of Global Partnerships

NEW YORK - July 10, 2025 - Nielsen, the global leader in audience measurement, data and analytics, today announced that it appointed Richard Pacheco as head of ...

10/07/2025

Sponsored: Robotic Deployments Are Transforming Local News

Local newscasts don't exist in a vacuum. News directors and station management constantly evaluate what's working, what isn't and perhaps most impor...

10/07/2025

Stuttgart Media University Upgrades Studio with Lawo mc56

Lawo has announced that Stuttgart Media University (Hochschule der Medien, HdM) has comprehensively modernized its central recording studio after selecting an I...

10/07/2025

SMPTE Opens Early Bird Registration for Media Technology Summit

The Society of Motion Picture and Television Engineers (SMPTE) has opened early-bird registration for the Media Technology Summit, which will take place in a ne...

10/07/2025

TNDV Television Launches Aspiration 35 to Support Cinematic Workflows

NASHVILLE, Tenn. TNDV Television has launched Aspiration 35, a new version of its 40-foot Aspiration truck reimagined for cinematic multicamera productions....

10/07/2025

Key Code Education Launches Beginner, Intermediate Training Courses

BURBANK, Calif. Key Code Education, a provider of instructor-led postproduction training, is growing its curriculum with new programs for beginner and intermedi...

10/07/2025

Actus Digital to Show Actus X Intelligent Monitoring With AI at IBC2025

HACKENSACK, N.J. Actus Digital will demonstrate how broadcasters can transform compliance monitoring from a necessary expense into a strategic revenue driver at...

10/07/2025

Comments on FCC Ownership Rules Due in August

The Federal Register has published a summary of the Federal Communications Commission's Public Notice seeking comments on its ownership rules that lists a d...

10/07/2025

Netflix Presents the Official Trailer for 'Superestar'

Back to All News Netflix Presents the Official Trailer for SuperestarPlay Video Play Video Entertainment 10 July 2025 GlobalSpain Link copied to clipboard...

10/07/2025

From Terabytes to Turnkey: AI-Powered Climate Models Go Mainstream

In the race to understand our planet's changing climate, speed and accuracy are everything. But today's most widely used climate simulators often strugg...

10/07/2025

Indonesia on Track to Achieve Sovereign AI Goals With NVIDIA, Cisco and IOH

As one of the world's largest emerging markets, Indonesia is making strides toward its Golden 2045 Vision - an initiative tapping digital technologies and...

10/07/2025

VEON and Cohen Circle Secure Investor Commitments for Kyivstar Listing

10 Jul 2025 VEON and Cohen Circle Secure Investor Commitments for Kyivstar Listing Kyiv, New York, Dubai, and Philadelphia - July 10, 2025 - VEON Ltd. (Nasdaq:...

10/07/2025

5G for All? What the DFL's Use of Easy5G, RefCam Could Mean for Events in the Future

5G for all? What the DFL's use of Easy5G and RefCam could mean for events in...

10/07/2025

Save the Date: PGA TOUR Studios Welcomes SVG Remote Production Summit on Oct 14-15

Save the Date: PGA TOUR Studios Welcomes SVG Remote Production Summit on Oct 14-...

10/07/2025

Cloud on the Road: How Remote-Production-Service Providers Are Adapting to a New Era

Cloud on the Road: How Remote-Production-Service Providers Are Adapting to a New...

10/07/2025

Seattle Kraken's Ryan Schaber on the NHL Team Taking Live Game Productions In-House

Seattle Kraken's Ryan Schaber on the NHL Team Taking Live Game Productions I...

10/07/2025

FOX Sports Reboots Small Control Room in Los Angeles as Hub for Vertical-First Production

FOX Sports Reboots Small Control Room in Los Angeles as Hub for Vertical-First P...

10/07/2025

SVG Sit-Down: MSE's Zach Leonsis, ViewLift's Rick Allen Go Deep on Joint Venture Targeting Local-Sports-Media Market

SVG Sit-Down: MSE's Zach Leonsis, ViewLift's Rick Allen Go Deep on Joint...

10/07/2025

From Treehouses to the Deep Sea: A First Look at Sky Kids New Adventures

Thursday 10 July 2025 The Very Small Creatures Jaime's Treetop Tales Emerald BooSnoo! Christmas Mashup Pip & Posy's Spooktacular Party The Very Sm...

10/07/2025

Millions of Sky customers set to enjoy even bigger rewards as Sky VIP loyalty programme gets a major upgrade

Thursday 10 July 2025 Brand new rewards are coming to Sky customers, with free ...