Navigation Links
Key to lung cancer chemo resistance revealed

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.

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.
'"/>

Source:Johns Hopkins Medical Institutions


Related biology news :

1. Viral DNA sequence a possible trigger for breast cancer
2. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
3. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
4. Columbia research lifts major hurdle to gene therapy for cancer
5. Combination therapy boosts effectiveness of telomere-directed cancer cell death
6. Mitochondrial DNA mutations play significant role in prostate cancer
7. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
8. BRCA1 causes ovarian cancer through indirect, biochemical route
9. Researchers identify target for cancer drugs
10. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.
11. First atlas of key brain genes could speed research on cancer, neurological diseases

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... 5, 2017  The Allen Institute for Cell Science ... a one-of-a-kind portal and dynamic digital window into the ... the first application of deep learning to create predictive ... lines and a growing suite of powerful tools. The ... and future publicly available resources created and shared by ...
(Date:3/30/2017)... -- On April 6-7, 2017, Sequencing.com will host the world,s ... at Microsoft,s headquarters in Redmond, Washington ... health and wellness apps that provide a unique, personalized ... is the first hackathon for personal genomics and the ... the genomics, tech and health industries are sending teams ...
(Date:3/27/2017)... N.Y. , March 27, 2017  Catholic ... Information and Management Systems Society (HIMSS) Analytics for ... EMR Adoption Model sm . In addition, CHS ... of U.S. hospitals using an electronic medical record ... for its high level of EMR usage in ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... ... genomics analysis platform specifically designed for life science researchers to analyze and ... researcher Rosalind Franklin, who made a major contribution to the discovery of ...
(Date:10/11/2017)... ... , ... ComplianceOnline’s Medical Device Summit is back for its 4th year. The ... Francisco, CA. The Summit brings together current and former FDA office bearers, regulators, industry ... officials from around the world to address key issues in device compliance, quality and ...
(Date:10/11/2017)... ... October 11, 2017 , ... Disappearing forests and increased emissions are the main ... people each year. Especially those living in larger cities are affected by air pollution ... of the most pollution-affected countries globally - decided to take action. , “I knew ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... (ADC) therapeutics, today confirmed licensing rights that give it exclusive global access ... developed in collaboration with Children’s Hospital Los Angeles (CHLA). Additionally, an ...
Breaking Biology Technology: