Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia
Despite the promise of the gene KRAS as a target for treating lung cancer, finding effective therapies has been challenging. Now researchers are traveling down the pathway to find what makes KRAS cancerous.
A new study from researchers at the University of Michigan Comprehensive Cancer Center sheds light on the KRAS pathway with a potential target that might have more success at stopping lung cancer growth.
The researchers found that a protein called FADD picks up a phosphate for a specific amino acid when KRAS is active, a process called phosphorylation. They engineered mouse models of lung cancer. In one set, they turned on KRAS and deleted FADD from the mouse's genome. In another set, they turned on KRAS and left FADD to work normally. The mice with deleted FADD did not get tumors, despite having active KRAS.
Phosphorylation happens to FADD through a protein called casein kinase 1-alpha, or CK1-alpha. So the researchers took the KRAS mouse model and deleted CK1-alpha from the genome. FADD was left alone. They found that in the absence of CK1-alpha, FADD never gets phosphorylated and the mice never get tumors despite having activated KRAS.
"We don't have effective ways of targeting KRAS directly, so we have to go downstream to attack. This study shows that casein kinase 1-alpha is a bona fide target for treatment of KRAS-mutated lung cancer," says corresponding study author Alnawaz Rehemtulla, Ph.D., Ruth Tuttle Freeman Research Professor of radiation oncology and radiology and co-director of the Center for Molecular Imaging at the University of Michigan Medical School.
Up to a quarter of lung cancers involve mutations in KRAS. No inhibitors of KRAS are currently available.
"Figuring out how KRAS causes cells to divide is important and gives us potential avenues for blocking the downstream activity and inhibiting lung tumor growth," Rehemtulla says.
The study is published on the cover of the Jan. 27 issue of Science Signaling.
A CK1-alpha inhibitor was used in this study and is currently being developed in laboratory settings. More work is needed before any potential clinical testing can begin.
Explore further: Enzyme may be key to cancer progression in many tumors
More information: Science Signaling, Vol. 8, No. 361, Jan. 27, 2015, DOI: 10.1126/scisignal.2005607
Medical Xpress on facebook
Related Stories
Enzyme may be key to cancer progression in many tumors
Nov 26, 2014
Mutations in the KRAS gene have long been known to cause cancer, and about one third of solid tumors have KRAS mutations or mutations in the KRAS pathway. KRAS promotes cancer formation not only by driving ...
Scientists identify possible KRAS downstream target for pancreatic cancer therapy
May 28, 2013
While the mutated KRAS oncogene is associated with many cancers, it has not yet been successfully targeted by a therapeutic agent. Scientists are trying to find another way to target the gene by blocking signals from another ...
Regulation of cancer-causing protein could lead to new therapeutic targets
Dec 16, 2013
Researchers with the Cincinnati Cancer Center (CCC) and the University of Cincinnati (UC) Cancer Institute have discovered a new regulation for the cancer-causing protein KRas which may help with the development of targeted ...
Gene linked to pancreatic cancer growth, study finds
Jan 31, 2012
A mutant protein found in nearly all pancreatic cancers plays a role not only in the cancer's development but in its continued growth, according to a new study from University of Michigan Comprehensive Cancer ...
Combination therapies for drug-resistant cancers
Oct 10, 2011
Some cancers can be effectively treated with drugs inhibiting proteins known as receptor tyrosine kinases, but not those cancers caused by mutations in the KRAS gene. A team of researchers led by Jeffrey Engelman, at Massachusetts ...
Recommended for you
Drug combo suppresses growth of late-stage prostate cancer tumors
10 minutes ago
Low doses of metformin, a widely used diabetes medication, and a gene inhibitor known as BI2536 can successfully halt the growth of late-stage prostate cancer tumors, a Purdue University study finds.
Prostate cancer: Androgen receptor activates different genes when bound to antiandrogens
1 hour ago
The androgen receptor in prostate cancer cells can activate different sets of genes depending on whether it binds with an androgen hormone or an antiandrogen drug, according to a new study led by researchers ...
Targeted MRI / ultrasound beats standard biopsy to detect high-risk prostate cancer
3 hours ago
Targeted biopsy using new fusion technology that combines magnetic resonance imaging (MRI) with ultrasound is more effective than standard biopsy in detecting high-risk prostate cancer, according to a large-scale study published ...
Researchers find potential anti-cancer use for anti-epilepsy drug
4 hours ago
Scientists at the University of York have discovered that a drug used widely to combat epilepsy has the potential to reduce the growth and spread of breast cancer.
Inherited gene variation helps explain drug toxicity in patients of East Asian ancestry
6 hours ago
About 10 percent of young leukemia patients of East Asian ancestry inherit a gene variation that is associated with reduced tolerance of a drug that is indispensable for curing acute lymphoblastic leukemia (ALL), the most ...
Inhibiting CDK6 prevents leukemic relapse
6 hours ago
Despite enormous progress in cancer therapy, many patients still relapse because their treatment addresses the symptoms of the disease rather than the cause, the so-called stem cells. Work in the group of ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here to reset your password.
Sign in to get notified via email when new comments are made.
© Medical Xpress 2011-2014, Science X network
Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia
Despite the promise of the gene KRAS as a target for treating lung cancer, finding effective therapies has been challenging. Now researchers are traveling down the pathway to find what makes KRAS cancerous.
A new study from researchers at the University of Michigan Comprehensive Cancer Center sheds light on the KRAS pathway with a potential target that might have more success at stopping lung cancer growth.
The researchers found that a protein called FADD picks up a phosphate for a specific amino acid when KRAS is active, a process called phosphorylation. They engineered mouse models of lung cancer. In one set, they turned on KRAS and deleted FADD from the mouse's genome. In another set, they turned on KRAS and left FADD to work normally. The mice with deleted FADD did not get tumors, despite having active KRAS.
Phosphorylation happens to FADD through a protein called casein kinase 1-alpha, or CK1-alpha. So the researchers took the KRAS mouse model and deleted CK1-alpha from the genome. FADD was left alone. They found that in the absence of CK1-alpha, FADD never gets phosphorylated and the mice never get tumors despite having activated KRAS.
"We don't have effective ways of targeting KRAS directly, so we have to go downstream to attack. This study shows that casein kinase 1-alpha is a bona fide target for treatment of KRAS-mutated lung cancer," says corresponding study author Alnawaz Rehemtulla, Ph.D., Ruth Tuttle Freeman Research Professor of radiation oncology and radiology and co-director of the Center for Molecular Imaging at the University of Michigan Medical School.
Up to a quarter of lung cancers involve mutations in KRAS. No inhibitors of KRAS are currently available.
"Figuring out how KRAS causes cells to divide is important and gives us potential avenues for blocking the downstream activity and inhibiting lung tumor growth," Rehemtulla says.
The study is published on the cover of the Jan. 27 issue of Science Signaling.
A CK1-alpha inhibitor was used in this study and is currently being developed in laboratory settings. More work is needed before any potential clinical testing can begin.
Explore further: Enzyme may be key to cancer progression in many tumors
More information: Science Signaling, Vol. 8, No. 361, Jan. 27, 2015, DOI: 10.1126/scisignal.2005607
Medical Xpress on facebook
Related Stories
Enzyme may be key to cancer progression in many tumors
Nov 26, 2014
Mutations in the KRAS gene have long been known to cause cancer, and about one third of solid tumors have KRAS mutations or mutations in the KRAS pathway. KRAS promotes cancer formation not only by driving ...
Scientists identify possible KRAS downstream target for pancreatic cancer therapy
May 28, 2013
While the mutated KRAS oncogene is associated with many cancers, it has not yet been successfully targeted by a therapeutic agent. Scientists are trying to find another way to target the gene by blocking signals from another ...
Regulation of cancer-causing protein could lead to new therapeutic targets
Dec 16, 2013
Researchers with the Cincinnati Cancer Center (CCC) and the University of Cincinnati (UC) Cancer Institute have discovered a new regulation for the cancer-causing protein KRas which may help with the development of targeted ...
Gene linked to pancreatic cancer growth, study finds
Jan 31, 2012
A mutant protein found in nearly all pancreatic cancers plays a role not only in the cancer's development but in its continued growth, according to a new study from University of Michigan Comprehensive Cancer ...
Combination therapies for drug-resistant cancers
Oct 10, 2011
Some cancers can be effectively treated with drugs inhibiting proteins known as receptor tyrosine kinases, but not those cancers caused by mutations in the KRAS gene. A team of researchers led by Jeffrey Engelman, at Massachusetts ...
Recommended for you
Drug combo suppresses growth of late-stage prostate cancer tumors
10 minutes ago
Low doses of metformin, a widely used diabetes medication, and a gene inhibitor known as BI2536 can successfully halt the growth of late-stage prostate cancer tumors, a Purdue University study finds.
Prostate cancer: Androgen receptor activates different genes when bound to antiandrogens
1 hour ago
The androgen receptor in prostate cancer cells can activate different sets of genes depending on whether it binds with an androgen hormone or an antiandrogen drug, according to a new study led by researchers ...
Targeted MRI / ultrasound beats standard biopsy to detect high-risk prostate cancer
3 hours ago
Targeted biopsy using new fusion technology that combines magnetic resonance imaging (MRI) with ultrasound is more effective than standard biopsy in detecting high-risk prostate cancer, according to a large-scale study published ...
Researchers find potential anti-cancer use for anti-epilepsy drug
4 hours ago
Scientists at the University of York have discovered that a drug used widely to combat epilepsy has the potential to reduce the growth and spread of breast cancer.
Inherited gene variation helps explain drug toxicity in patients of East Asian ancestry
6 hours ago
About 10 percent of young leukemia patients of East Asian ancestry inherit a gene variation that is associated with reduced tolerance of a drug that is indispensable for curing acute lymphoblastic leukemia (ALL), the most ...
Inhibiting CDK6 prevents leukemic relapse
6 hours ago
Despite enormous progress in cancer therapy, many patients still relapse because their treatment addresses the symptoms of the disease rather than the cause, the so-called stem cells. Work in the group of ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here
to reset your password.
Sign in to get notified via email when new comments are made.
© Medical Xpress 2011-2014, Science X network
0 comments:
Post a Comment