Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Johns Hopkins gene hunters pinpoint new cancer gene target

12.03.2004


Scientists at the Johns Hopkins Kimmel Cancer Center and Howard Hughes Medical Institute have found mutations in a gene linked to the progression of colon and other cancers. The research findings, published online in the March 11 issue of Science, may lead to new therapies and diagnostic tests that target this gene.



The gene in which the mutations have been found, called PIK3CA, is part of a family of genes encoding lipid kinases, enzymes that modify fatty molecules and direct cells to grow, change shape and move. Although scientists have been studying the biochemical properties of this family of genes for more than a decade, until now, no study revealed that they were mutated in cancer.

Kinases have been the focus of recent drug development strategies, with some kinase-inhibiting compounds, such as Gleevec and Herceptin, already being used clinically to inhibit tumor growth.


"These findings open the door to developing specific therapies that may prove useful for the treatment of cancers with mutations in PIK3CA," says Victor Velculescu, M.D., Ph.D., assistant professor of oncology and senior author of the research.

In their current experiments, the scientists sequenced the molecular code of the genes in this lipid kinase family and found mistakes in the nucleotides, or DNA building blocks, in one particular gene, called PIK3CA. Each mistake is a result of one nucleotide being switched for another. PIK3CA mutations were found in 32 percent of colon cancer samples (74/234), as well as 27 percent (4/15) of glioblastomas, 25 percent (3/12) of gastric cancers, 8 percent (1/12) breast cancers and 4 percent (1/24) of lung cancers. By studying 76 additional premalignant colon tumors, the scientists found that PIK3CA mutations may occur at or near the time a tumor is about to invade other tissues.

The investigators demonstrated that the mutations increase PIK3CA kinase activity, which can start a cascade of cellular events that spark a normal cell to grow uncontrollably and become cancerous.

"We envision future cancer therapy as personalized, based on gene mutations in each patient’s tumor," says Velculescu. "This kind of information, gleaned from sequencing a patient’s tumor, means drugs could be targeted to just the right molecular pathway at just the right time and potentially be more effective with fewer side effects."

Most of the PIK3CA mutations described in the current paper are located in two DNA cancer "hot spots," thus making molecular diagnostic tests possibly easier to develop. "These mutations, added to a panel of existing markers for colon cancer developed in our laboratory, could help find cancers that would otherwise go undetected," says Yardena Samuels, Ph.D., postdoctoral fellow and first author of the study.

The researchers are now looking more closely at the role of PIK3CA in tumor development and are working on identifying compounds that could target tumors with mutations in this gene.

This research was funded by the Ludwig Trust, the Benjamin Baker Scholarship Fund, the EMBO Fellowship Fund and grants from the National Institutes of Health.

Other participants of this research include Zhenghe Wang, Alberto Bardelli, Natalie Silliman, Janine Ptak, Steve Szabo, Gregory J. Riggins, Kenneth W. Kinzler and Bert Vogelstein of the Johns Hopkins Kimmel Cancer Center and Howard Hughes Medical Institute; Hai Yan of Duke University Medical Center; Adi Gazdar of UT Southwestern Medical Center; Steven M. Powell of the University of Virginia Health System; and James K.V. Willson and Sanford Markowitz of the Howard Hughes Medical Institute and Ireland Cancer Center, University Hospitals of Cleveland and Case Western University.

Vanessa Wasta | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/

More articles from Health and Medicine:

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

nachricht Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases

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: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

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

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Scientists re-create brain neurons to study obesity and personalize treatment

20.04.2018 | Health and Medicine

Spider silk key to new bone-fixing composite

20.04.2018 | Materials Sciences

Clear as mud: Desiccation cracks help reveal the shape of water on Mars

20.04.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>