Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists tie several cancers to common 'oncogene engine'

14.06.2006
Discovery could unify treatment of different lethal malignancies

Researchers at Dana-Farber Cancer Institute report that a common "oncogene engine" – a small family of malfunctioning cell growth switches – drives several seemingly unrelated, lethal forms of cancer, including malignant melanoma. The finding suggests that it may be possible to attack these different cancers with the same therapy.

Reporting in the June issue of Cancer Cell, the scientists showed that a small transcription factor family, made up of several proteins that control the activity of key growth genes, functions abnormally in malignant melanoma, two forms of soft-tissue sarcomas, and a type of kidney cancer that mainly affects children. Still other cancers sharing the same causative mechanism may yet be found, the scientists said.

"One would have never thought of grouping these tumors together," said David E. Fisher, MD, PhD, a pediatric oncologist at Dana-Farber and Children's Hospital Boston, who is senior author of the paper. The lead author is Ian J. Davis, MD, PhD, of Dana-Farber and Children's Hospital Boston.

"The importance of this finding is that it suggests a common 'engine' is driving these seemingly unrelated cancers," Fisher said. "Therefore, it is plausible that common therapeutic strategies might be applied to the tumors as well." The newly grouped cancers – melanoma, clear cell sarcoma, alveolar soft part sarcoma, and pediatric renal carcinoma – are often lethal if surgery cannot completely remove them.

Dana-Farber researchers are already using these new insights in clinical trials of a cancer vaccine, GVAX, that previously has produced rare but dramatic responses in some patients with advanced melanoma. "We have just opened a trial to offer the same vaccine to patients with all of the other cancers in this related family," said Fisher. "Prior to this, virtually no rational experimental treatments were available for these diseases, and patients have already started coming from throughout the country to enlist in our trial."

The transcription factor family is collectively known as MiT. Its kingpin, a protein called MITF, is needed by the body to develop normally functioning melanocytes, the pigment-producing cells of the skin and hair. Mutations that disable MITF cause lack of pigment, as in albinism, but when the gene for MITF is amplified – too many copies in a cell – it can cause melanoma, because the growth genes that are regulated by MITF act like a stuck "on" switch for cell proliferation. Last year, investigators based at Dana-Farber (including Fisher and his colleagues) reported that the MITF gene is amplified in 20 percent of melanoma tumors.

In addition, Fisher and Scott R. Granter, MD, of Children's Hospital Boston – also an author of the Cancer Cell article – previously found that MITF was present in a dangerous type of soft-tissue tumor – clear cell sarcoma – that develops near muscles and tendons in teenagers and young adults. The scientists had been alerted to the possibility of MITF involvement because clear cell sarcoma tumors are sometimes pigmented – a process requiring the MITF transcription factor. In this form of sarcoma, Fisher explained, the MITF gene is overactivated by an abnormal joining, or fusion, of two other genes. MITF, in turn, is directly responsible for malignant growth and survival of the cells. Suppression of MITF by genetic means in the laboratory is lethal to clear cell sarcoma.

While no drug currently exists to directly suppress MITF, the identification of MITF's role opens a door to potential therapies because the researchers have identified some of the genes and proteins that MITF regulates that new drugs could be used to block. One of the targets is Bcl-2, which enables cancer cells to survive when the body has ordered them to self-destruct, and another is CDK-2, a protein that is often abnormal in cancer.

Related to MITF in the MiT transcription factor family are three proteins named TFEB, TFE3, and TFEC. One of them, TFEB, is known to be abnormal in certain kidney carcinomas in children, and TFE3 is involved in another rare soft-tissue tumor, alveolar soft part sarcoma, which tends to affect female children and young adults.

"It is now apparent that all of these tumors share this central family of oncogenes that are functionally interchangeable," said Fisher, who is also a professor of pediatrics at Harvard Medical School. His team demonstrated this point by showing that when tumors in mice were shrunk by disabling one of the transcription factors, replacing it with another member of the family re-started the tumor's growth. In the short term, clinicians will attempt to exploit this interconnectedness by using therapies that may be effective against one tumor to try to treat other tumors, said Fisher. "In the longer term, the focus is on targeting the real culprit – and that is the MiT transcription factors or their targets. There is lots of excitement, and I believe that is the way to really nail these tumors."

Janet Haley Dubow | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>