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 PET imaging tracks Zika virus infection, disease progression in mouse model
20.09.2017 | US Army Medical Research Institute of Infectious Diseases

nachricht 'Exciting' discovery on path to develop new type of vaccine to treat global viruses
18.09.2017 | University of Southampton

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: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>