Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hopkins scientists uncover role of Fanconi’s Anemia genes in pancreatic cancer

15.05.2003


Scientists at the Johns Hopkins Kimmel Cancer Center have identified three genes, long linked to a rare inherited disease known as Fanconi’s Anemia (FA), that now appear to play a role in many cases of pancreatic cancer.



All of the genes identified, when functioning normally, are part of the DNA repair process. The work is reported in the May 15, 2003 issue of Cancer Research.

"What we think we have is a new genetic cause of some cases, approximately 10 percent or more, of pancreatic cancers, one of the most lethal forms of cancer," according to Scott Kern, M.D., professor of oncology and pathology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and director of the study. The good news is that these genes offer new targets for improved treatment, he says.


The genes have all been associated with Fanconi’s Anemia. Those affected are born with only a single normal copy of one or more of the genes. Though they do not develop FA, these people often develop pancreatic cancer, usually in their 40s and 50s, about a decade earlier than average age of onset, according to Kern.

"The up side is that while these gene mutations cause a horrific disease, they may actually be the Achilles heel of the tumor and make these particular cancers more responsive to treatment," says Kern.

The culprit genes, including BRCA2, linked by other earlier studies to breast cancer, as well as two other genes FANCC and FANCG, appear to make pancreatic cancer cells highly susceptible to treatment with two FDA-approved cancer drugs mitomycin C and cisplatin. Human clinical trials are now being planned.

Normally, the genes are responsible for keeping DNA in good repair. As DNA is copied for cell replication, these genes compare the copies of DNA and fix any breaks. Mitomycin C and cisplatin work by causing the exact breaks these genes are supposed to repair. In the subset of patients whose pancreatic cancer is caused by mutations of these repair genes, the cancer cells are missing this repair mechanism making them unable to fix the breaks caused by the drugs, so the cancer cells should die, Kern says.

Both drugs are currently used in pancreatic cancer therapy, and though some remissions have been reported, the drugs have been largely ineffective. Kern suspects it’s a matter of a patient selection and dose.

Kern says preliminary laboratory and animal studies suggest low doses over a prolonged period of time may have the most benefit, and probably only in patients with FA gene mutations. He is now working with other investigators to develop clinical trials to study the drugs in patients with early onset disease, which may be caused by FA gene mutants.

In the study, the scientists examined a panel of human pancreatic cancers. They found mutations of FA-related genes in three of nine of tumor samples from patients aged 50 or younger. The researchers believe these mutations are common among the general population, estimating that about 1 in every 300 people have inherited a mutated copy of at least one FA gene.

"Our findings also tell us that cancers that appear to occur randomly in the population may not always really be so random," Kern says. "It is likely that the origin of many cancers could be traced back to similar inherited genetic mutations," says Kern.

People born with just one normal copy of the FA genes have an unfortunate head start on the cancer process, Kern says. If that one good copy is lost from dietary and/or environmental exposures, the cellular mistakes go unchecked, accelerating the initiation of cancer. He suspects these mutations could be responsible for a subset of other cancers as well, including certain breast, ovarian, and prostate cancers.

Fanconi’s Anemia occurs in less than 1 in 100,000 people, caused by the hereditary loss of both copies of an FA gene. People with FA are born with skeletal abnormalities and often develop cancers early in life. Until now, experts did not believe the loss of only one FA gene also was disease-related. "Something we thought was not causing disease, we now suspect causes one of the worst forms of cancer," says Kern.

Pancreatic cancer has one of the lowest survival rates among all cancers. Each year, approximately 30,300 Americans are diagnosed with the disease, and nearly 30,000 die. Often unresponsive to conventional therapies, pancreatic cancer is the fourth leading cause of cancer death.

In addition to Kern, other participants in this study were Michiel S. van der Heijden, Charles J. Yeo, and Ralph H. Hruban.


This research was funded by a National Cancer Institute gastro-intestinal SPORE (Specialized Projects of Research Excellence) grant.

Valerie Matthews Mehl | EurekAlert!
Further information:
http://www.hopkinsmedicine.org
http://www.hopkinskimmelcancercenter.org

More articles from Health and Medicine:

nachricht New approach towards an improved treatment of anxiety disorders
12.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

nachricht Researchers image atomic structure of important immune regulator
11.12.2018 | Brigham and Women's Hospital

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: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Innovative Infrared heat reduces energy consumption in coating packaging for food

12.12.2018 | Trade Fair News

New Foldable Drone Flies through Narrow Holes in Rescue Missions

12.12.2018 | Information Technology

Obtaining polyester from plant oil

12.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>