Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key to lung cancer chemo resistance revealed

12.10.2006
Scientists at Johns Hopkins have discovered how taking the brakes off a "detox" gene causes chemotherapy resistance in a common form of lung cancer.

Products made by a gene called NRF2 normally protect cells from environmental pollutants like cigarette smoke and diesel exhaust by absorbing the materials and pumping them out of the cell. Another gene called KEAP1 encodes products that stop this cleansing process. But lung cancer cells sabotage the expression of these same genes to block assault from chemotherapy drugs.

"What we're seeing is that lung cancer cells recruit and distort NRF2 and KEAP1 expression to help tumor cells evade the toxic effects of chemotherapy," says Shyam Biswal, Ph.D., associate professor at the Johns Hopkins Bloomberg School of Public Health and Kimmel Cancer Center, who published results of cell culture studies in the October 3, 2006 issue of PLoS Medicine.

Past studies have shown that NRF2 detoxifies cells by directing proteins to absorb and pump out pollutants and chemicals. The NRF2 gene makes a "trigger" protein which starts the production of other proteins and enzymes that sweep the cell clear of toxins. To halt the detox process, proteins manufactured by KEAP1 bind to the NRF2 triggers tagging them for destruction. In cancer cells, NRF2 activity runs amok, sweeping away all cellular toxins, including chemotherapy agents.

... more about:
»Chemo »KEAP1 »NRF2 »cancer cells »chemotherapy »lung cancer

Biswal says that blocking NRF2 activity could improve the effectiveness of standard chemotherapy drugs, particularly platinum-based compounds widely used for lung cancer.

In Biswal's study, half of 12 lung cancer cell lines and 10 of 54 tissue samples from non-small cell lung cancer patients had mutations in the KEAP1 gene rendering it inactive and unable to keep NRF2 activity in check. In addition, half of the tissue samples were missing one copy of the KEAP1 gene - cells usually have two copies of each gene. No missing genes or mutations were observed in normal lung tissues from the same patients.

NRF2 activity along with its cleansing proteins and enzymes were higher in tumor samples than normal cells, according to the researchers. Their cell culture tests also show that cancer cells with KEAP1 mutations are more resistant to chemotherapy drugs than normal lung cells.

Tumor samples with normal KEAP1 genes also show increased levels of NRF2 and its enzymes, suggesting other ways of dismantling KEAP1, such as splicing the gene to make a shortened, ineffective protein, he said.

The researchers plan to confirm their findings with a larger set of samples and then to screen for appropriate drugs. Funding for the study was provided by the National Cancer Institute Lung SPORE (Specialized Program of Research Excellence), National Heart Lung and Blood Institute, National Institute of Environmental Health Sciences Center, National Institute of Health, and the Flight Attendant Medical Research Institution.

Vanessa Wasta | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: Chemo KEAP1 NRF2 cancer cells chemotherapy lung cancer

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

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...

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

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>