Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify protein critical to melanoma growth

21.12.2004


Researchers at Dana-Farber Cancer Institute and Children’s Hospital Boston have discovered that malignant melanoma, the potentially lethal skin cancer, can’t grow without a steady supply of a protein that normal cells can do without.



The findings, which are published in the December issue of Cancer Cell, suggest that drugs that cut off melanoma cells’ supply of the protein, called CDK2, might curb the growth of the dangerous skin cancer in patients, and with relatively low toxicity. In theory, such a drug would leave normal cells unharmed and have many fewer side effects compared to standard chemotherapy.

Working with melanoma cells grown in the laboratory, the researchers, led by David E. Fisher, MD, PhD, Director of the Melanoma Program at Dana-Farber and the paper’s senior author, showed that adding a chemical that quashed the activity of CDK2, the gene that manufactures CDK2 protein, dramatically slowed the growth and proliferation of the cancer cells. Unlike conventional chemotherapy drugs, a CDK2 inhibitor drug wouldn’t be aimed at killing melanoma cells, only halting their growth.


Fisher said that CDK2-inhibiting drugs exist, and he hopes that the research results will soon lead to clinical trials of them in patients with melanoma.

The study’s lead author is Jinyan Du, PhD, who carried out the project while working as a student in Fisher’s lab at Dana-Farber. Fisher is also a pediatric oncologist at Dana-Farber/Children’s Hospital Cancer Care.

The CDK2 gene and its protein (an enzyme) are one of several regulators of the cell cycle: That is, they help determine when a cell should be "resting" and when it should begin dividing to make more of itself. When cells become malignant, it is in part because their normal controls on growth and division are disabled, and they proliferate abnormally. Overactive CDK2 has been found in many types of cancer, making it a prime candidate for designer drugs that would turn down CDK2 activity and, it was hoped, slow the runaway growth of cancer cells.

Recent research, however, had thrown cold water on the notion. Studies have shown that tumor cells in a variety of cancers weren’t dependent on CDK2 for growth. Thus, blocking its activity had little effect on the out-of-control cells.

The scientist’s report today is all the more striking, because it reveals that melanoma does require the CDK2 enzyme for growth. Why this is so isn’t clear, but the finding revives the strategy of using CDK2 inhibitors as a potential treatment – even if only for this one form of cancer. And, since it’s been previously shown that normal cells can divide and grow normally without CDK2 (other types of CDK molecules apparently can take over the job) "this is good news, because it means there may be little toxicity to a person who would receive a CDK2 inhibitor to treat melanoma," says Fisher, who is also an associate professor of pediatrics at Harvard Medical School.

Melanoma will cause about 7,900 deaths this year in the United States, according to the American Cancer Society. Its incidence has been rising rapidly over the past several decades: about 55,000 cases are expected in 2004. Most cases caught early can be cured, but if melanoma cells penetrate the skin deeply, the cancer is highly prone to spread with life-threatening consequences despite treatment with surgery, chemotherapy and radiation.

The new findings stem from Fisher’s longtime work on a gene called MITF that regulates the development of skin pigment-producing cells called melanocytes. Regulatory genes like MITF act on other genes in a chain-of-command fashion. When Fisher’s group looked for genes regulated by MITF, they found a pigment gene called SILVER, and they noted that, surprisingly, it was located just a stone’s throw, genetically, from CDK2 on the chromosome.

"It was dumb luck," says Fisher, and it led him and his colleagues to recognize that both SILVER and CDK2 were under the control of MITF. In all other body cells besides melanocytes, CDK2 is not subservient to MITF: To the researchers this was an important clue. "If the control of CDK2 expression is so different in the development of melanocytes, then maybe the requirement for CDK2 in melanoma is different than in other cancers," he says – and the new findings confirm this idea.

The fact that melanoma cells, unlike other cancer cells, become "overdependent" on the CDK2 protein while normal cells don’t need much of it provides a "therapeutic window." That is, a drug that suppresses melanoma growth by shutting down CDK2 in theory could control the cancer yet have little toxic effect on the body.

In addition to Fisher and Du, the paper’s other authors include researchers from the Broad Institute at the Massachusetts Institute of Technology and Harvard University, MIT, and Massachusetts General Hospital. The research was funded by the National Institutes of Health.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

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

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Midwife and signpost for photons

11.12.2017 | Physics and Astronomy

How do megacities impact coastal seas? Searching for evidence in Chinese marginal seas

11.12.2017 | Earth Sciences

PhoxTroT: Optical Interconnect Technologies Revolutionized Data Centers and HPC Systems

11.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>