Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Deadliest Cancers May Respond to New Drug Treatment Strategy

Published: Monday, July 22, 2013
Last Updated: Monday, July 22, 2013
Bookmark and Share
Researchers have found a way to knock down cancers caused by a tumor-driving protein called “myc,” paving the way for clinical trials.

Myc acts somewhat like a master switch within cells to foster uncontrolled growth. Until now, it has been impossible to target with drugs.

The discovery of an unexpected biochemical link within tumor cells should lead to clinical trials for experimental drug treatments that indirectly target myc and that already are being evaluated in human studies, the researchers said.

UCSF Helen Diller Family Comprehensive Cancer Center scientists led by Davide Ruggero, PhD, and Kevan Shokat, PhD, used one such drug to stop tumor growth in a mouse model of myc-driven lymphoma and multiple myeloma types of blood cancer.

Their study is published online in Proceedings of the National Academy of Sciences (PNAS).

Previously Ineffective Drug Therapies

Unrestrained myc activity is a major player in many cancers, including cancers of the lung, colon, breast, brain, prostate and blood. Abnormal myc in cancer often is associated with poor treatment outcomes, including death.

Although other cancer-associated proteins have been successfully attacked with targeted therapies in recent years, the myc protein has continued to elude efforts to develop drugs that target it. In the PNAS paper, the UCSF researchers describe how they found a way to indirectly, but effectively, target myc-driven tumors.

The researchers discovered that cancerous myc can be thwarted by treatment that targets a specific function performed by another protein, called mTOR. The mTOR protein is part of a different biochemical pathway controlling protein production and metabolism, one that also often takes a crooked turn in tumors.
 
Protein Production in Cancer Is Promising Target

Ruggero has for several years been probing the ability of tumor cells to make extraordinary amounts of protein to sustain their rapid growth and immortality. He also explores ways to target this excess protein production in cancer.

“One of the major and immediate downstream effects of myc activation is a dramatic increase in the capacity of affected cells to make protein,” Ruggero said “This, in turn, leads to increased cell survival and proliferation, and to unstable genomes that foster additional mutations that turn these abnormal cells into tumor cells.”

In earlier studies, Ruggero found that myc not only drives protein production, but also that myc-driven cancer cells become absolutely dependent upon this ability to make abnormal amounts of protein. When he genetically manipulated myc-driven cancer cells to slow protein production, they committed suicide, as abnormal cells are supposed to do for the greater good.

“Tumors become addicted to excessive protein production, and mutant myc itself seems to depends on it,” Ruggero said.

When present in tumors, both abnormal myc and abnormal mTOR are known to be able to rev up protein production and to foster cell growth. However, it was unclear how this myc-driven protein production could be therapeutically targeted, Ruggero said.

In the new study, the UCSF team discovered that myc relies in part on mTOR to secure its protein supply. First mTOR disables a protein that acts as a tumor suppressor, called 4EBP1. The disabling of 4EBP1 releases normal constraints on protein production within the cell. Previously, other molecular actors had been thought to play leading roles in triggering excess protein production directed by myc.

“The discovery that myc converges on the same downstream path as mTOR was surprising to us,” Ruggero said.

Zeroing In on the mTOR Protein

The researchers targeted mTOR with an experimental drug based on a prototype first designed by Shokat, a chemist and an expert in designing molecules to target this type of protein, called a kinase. In the mice, drug treatment caused a shutdown of excess protein production in myc-driven cancer cells. Myc no longer was able to drive tumor growth, cancer cells committed suicide, and the treated mice survived longer.

“In the clinic, we frequently test myc levels in patients’ tumors, for disease prognosis and to predict treatment response,” said Michael Pourdehnad, MD, a clinical oncologist at UCSF with Ruggero's lab and the first author of the study. “Yet, the lack of specific therapies to target myc-driven cancers is frustrating. Our discovery may provide a novel solution for these patients.”

“We are excited by the work of Dr. Pourdehnad and colleagues and believe these results are an important advance in understanding the role of myc pathway dysregulation in multiple myeloma, and ultimately allow for the development of therapeutic strategies to address it,” said Jeffrey Wolf, MD, a UCSF blood disorder specialist and director of the Stephen and Nancy Grand Multiple Myeloma Translational Initiative at UCSF, a sponsor of the research.

The drug used in the study, called MLN0128, is made by Millennium, an independently operated subsidiary of Takeda Pharmaceutical Co., Ltd., based in Cambridge, Mass., and it is being evaluated in clinical trials to treat a variety of cancers. It had not previously been viewed as a weapon against myc-driven tumors, according to the UCSF researchers.

Currently sold drugs directed against mTOR do not inhibit its ability to target 4EBP1, which Ruggero refers to as a “master regulator” of protein production.

“This is a unique therapeutic approach to make myc druggable in the clinic,” Shokat said.

Additional co-authors of the study are UCSF graduate students Morgan Truitt and Greg Ducker, and Imran Siddiqi, MD, PhD, a pathologist at the University of Southern California. Additional funds for the research were awarded by the National Institutes of Health (Grants R01CA154916 and R01 CA140456), and the Waxman Foundation. Shokat is supported by the Howard Hughes Medical Institute and Truitt is supported in part by an HHMI fellowship. The authors declare no conflict of interest in this research.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,100+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
Thursday, May 19, 2016
An E.coli Detector May be in Your Hands Soon
Hand-held device that can be used to detect a variety of pathogens—including foodborne pathogens like E. coli—at all stages in the food supply chain, from fields to restaurants may be available soon.
Monday, May 16, 2016
Fructose Alters Hundreds of Brain Genes
UCLA scientists report that diet rich in omega-3 fatty acids can reverse the damage.
Tuesday, April 26, 2016
Study Yields the Key to Effective Personalized Medicine
A team of UCLA bioengineers and surgeons has taken a major step toward making personalized medicine a reality.
Monday, April 11, 2016
Tracking RNA in Live Cells
Technique may open doors to new treatments for many conditions, from cancer to autism.
Friday, March 18, 2016
Cat Stem Cell Therapy Gives Humans Hope
By the time Bob the cat came to the UC Davis veterinary hospital, he had used up most of his nine lives.
Monday, February 08, 2016
Crowdfunding the Fight Against Cancer
From budding social causes to groundbreaking businesses to the next big band, crowdfunding has helped connect countless worthy projects with like-minded people willing to support their efforts, even in small ways. But could crowdfunding help fight cancer?
Monday, February 08, 2016
Toxic Pollutants Found in Fish Across the World's Oceans
Scripps researchers' analysis shows highly variable pollutant concentrations in fish meat.
Friday, January 29, 2016
Key Enzyme in Pierce’s Disease Grapevine Damage Uncovered
UC Davis plant scientists have identified an enzyme that appears to play a key role in the insect-transmitted bacterial infection of grapevines with Pierce’s disease, which annually costs California’s grape and wine industries more than $100 million.
Wednesday, January 13, 2016
Science Magazine Names CRISPR ‘Breakthrough of the Year’
In its year-end issue, the journal Science chose the CRISPR genome-editing technology invented at UC Berkeley 2015’s Breakthrough of the Year.
Monday, December 21, 2015
Genome Sequencing May Save California's Legendary Sugar Pine
The genome of California’s legendary sugar pine, which naturalist John Muir declared to be “king of the conifers” more than a century ago, has been sequenced by a research team led by UC Davis scientists.
Thursday, December 17, 2015
Cellular “ORACLs” to Aid Drug Discovery
New approach for finding therapeutics is inspired by face-recognition software.
Wednesday, December 16, 2015
New Virus Disovered, Linked To Hepatitis C
Study is first to reveal entire genetic makeup of human pegivirus 2.
Tuesday, December 15, 2015
CRISPR-Cas9 Helps Uncover Genetics of Exotic Organisms
A new study illustrates the ease with which CRISPR-Cas9 can knock out genes in exotic animals to learn how those genes control growth and development.
Friday, December 11, 2015
UC Davis Cracks the Walnut Genome
Scientists at the University of California, Davis, have for the first time sequenced the genome of a commercial walnut variety.
Friday, December 11, 2015
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
Grant Supports Project To Develop Simple Test To Screen For Cervical Cancer
UCLA Engineering announces funding from Bill and Melinda Gates Foundation.
Injecting New Life into Old Antibiotics
A new fully synthetic way to make a class of antibiotics called macrolides from simple building blocks is set to open up a new front in the fight against antimicrobial drug resistance.
Insight into Bacterial Resilience and Antibiotic Targets
Variant of CRISPR technology paired with computerized imaging reveals essential gene networks in bacteria.
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Alzheimer’s Protein Serves as Natural Antibiotic
Alzheimer's-associated amyloid plaques may be part of natural process to trap microbes, findings suggest new therapeutic strategies.
Slime Mold Reveals Clues to Immune Cells’ Directional Abilities
Study from UC San Diego identifies a protein involved in the directional ability of a slime mold.
How Do You Kill A Malaria Parasite?
Drexel University scientists have discovered an unusual mechanism for how two new antimalarial drugs operate: They give the parasite’s skin a boost in cholesterol, making it unable to traverse the narrow labyrinths of the human bloodstream. The drugs also seem to trick the parasite into reproducing prematurely.
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Supressing Intenstinal Analphylaxis in Peanut Allergy
Study from National Jewish Health shows that blockade of histamine receptors suppresses intestinal anaphylaxis in peanut allergy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,100+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!