Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumor-like spheres help scientists discover smarter cancer drugs

14.05.2018

Cancer is a disease often driven by mutations in genes. As researchers learn more about these genes, and the proteins they code for, they are seeking smarter drugs to target them. The ultimate goal is to find ways to stop cancer cells from multiplying out of control, thereby blocking the growth and spread of tumors.

Now researchers from The Scripps Research Institute are reporting an innovative new method to screen for potential cancer drugs. The technique makes use of tiny, three-dimensional ball-like aggregates of cells called spheroids.


The researchers used a technique called confocal microscopy to confirm that the cell lines were forming spheres. Here is the BxPC-3-KRASWT cell line.

Credit: Kota et. al./The Scripps Research Institute


The researchers used a technique called confocal microscopy to confirm that the cell lines were forming spheres. Here is the BxPC-3-KRASG12V cell line.

Credit: Kota et. al./The Scripps Research Institute

These structures can be used to interrogate hundreds or even thousands of compounds rapidly using a technique called high throughput screening. In fact, by using this approach, the team has already identified one potential drug for an important cancer gene. The results were reported in the journal Oncogene.

"What's important about this research is that we're able to do studies using a form of cancer cells that is more physiologically relevant and better recapitulates how these cells appear in the body," says Timothy Spicer, director of Lead Identification Discovery Biology and High Throughput Screening on Scripps Research's Florida campus and one of the study's corresponding authors.

"Until now, most of the research to screen for cancer drugs has used cells that are growing flat on a plate," adds Louis Scampavia, director of HTS Chemistry and Technologies at Scripps Research and one of the study's co-authors. "With these 3-D spheroids, we emulate much more closely what's found in living tissues."

The spheroids are 100 to 600 microns in diameter-equivalent to the thickness of a few sheets of paper. In contrast to single layers of cells normally used to screen for drugs, which tend to all grow at the same rate because they get the same exposure to oxygen and nutrients, the spheroids mimic what might happen in a tumor: Some cells are on the outside and some are on the inside.

In the new paper, the researchers focused on a cancer-driving protein called KRAS. The KRAS gene and other members of the related RAS gene family are found to be mutated in nearly one-third of all cancers. They are common in lung cancer, colorectal cancer, and especially pancreatic cancer. In fact, up to 90 percent of pancreatic cancers are driven by KRAS mutations, and the investigators used pancreatic cancer cell lines for the current study.

"In the past, KRAS has been a very tricky protein to target. People have spent several decades trying, but so far there has been little success," says Joseph Kissil, PhD, professor at Scripps Research Medicine and the other co-corresponding author. "The KRAS protein is relatively small, and that's made it hard to attack it directly. But the method of screening that we used in this study allowed us to come at the question in a different way."

The investigators performed what is called a phenotypic screen, which means they were looking for drugs that had an effect on cell growth, but didn't have a preconceived idea about how they might work. "We came at this in an unbiased way," Kissil explains. "We were not trying to design something to attack a specific part of the KRAS protein. We were just looking for something that acted on some part of the pathway that's driving cell growth."

The investigators report in the new paper that they have already identified one compound that was previously not know to affect KRAS, called Proscillaridin A. The compound is similar to a class of drugs used to treat some heart conditions. Although the team says this particular drug is unlikely to be developed as a cancer treatment, it validates the approach of conducting drug screenings using spheroids. "It's unlikely we would have discovered this connection using standard 2-D methods," Scampavia says.

"From our perspective, this is a proof-of-principle study," Kissel adds. "It shows you can look at libraries of drugs that have already been approved for other diseases, and find drugs that may also work for cancer. In theory, you could use this screening method for any line of cancer cells, and any mutation you want."

"We would love to use this research to create a pipeline for new oncology drugs," Spicer concludes. "Many of the most promising compounds may be overlooked with 2-D screening. This study provides direct evidence that screening for drugs using 3-D structures of cancer cells may be more appropriate."

###

Other authors of the study, "A Novel 3-dimensional High Throughput Screening Approach Identifies Inducers of a Mutant KRAS Selective Lethal Phenotype," were Smitha Kota, Shurong Hou, William Guerrant, Franck Madoux, Scott Troutman, Virneliz Fernandez-Vega, Nina Alekseeva and Neeharika Madala of Scripps Research.

This work was supported in part by the National Cancer Institute of the National Institutes of Health (grants R33CA206949 and CA124495).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates and 18 members of the National Academies of Science, Engineering or Medicine-work toward their next discoveries. The institute's graduate program, which awards doctoral degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu/.

Media Contact

Stacey Singer DeLoye
sdeloye@scripps.edu
561-228-2551

 @scrippsresearch

http://www.scripps.edu 

Stacey Singer DeLoye | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41388-018-0257-5

Further reports about: KRAS TSRI cancer cells cancer drugs cell growth drugs pancreatic pancreatic cancer

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>