New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors

August 13, 2012, Journal of Clinical Investigation

Aberrant regulation of cell growth pathways is required for normal cells to become cancerous, and in many types of cancer, cell growth is driven by a group of enzymes known as receptor tyrosine kinases (RTKs). The RTK epidermal growth factor receptor (EGFR) is overexpressed in over 30% of breast cancers; however, drugs that target RTKs, known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. Researchers believe that the cancer cells escape TKIs by circumventing the RTKs and utilizing other enzymes that are not TKI-sensitive.

In the current issue of the , two groups identify a pair of related oncogenes, FAM83A and B, which allow to survive TKI treatment. Researchers led by Mina Bissell at the Lawrence Berkeley National Laboratory in Berkeley, CA performed a screen of human breast cancer cell lines to identify genes that make cancer cells resistant to EGFR TKIs.

Bissell and colleagues determined that increased expression of FAM83A increases proliferation and invasion, while decreased expression delays tumor growth in mice and renders cancer cells sensitive to TKIs.

At Case Western Reserve Medical School in Cleveland, OH, Mark Jackson and colleagues identified FAM83B as a gene that allows normal human mammary cells to become malignant. Further, expression of FAM83A and B in human tumors was correlated with decreased overall survival. Taken together, these studies identify two genes that may serve as novel therapeutic targets.

In a companion piece, Steven Grant of the Medical College of Virginia discusses the impact of this research on the development of strategies to overcome resistance to currently available TKIs.

Explore further: PET scan with [11C]erlotinib may provide noninvasive method to identify TKI-responsive lung tumors

More information:
Identification of FAM83B as a novel intermediary in EGFR/RAS-mediated transformation, Journal of Clinical Investigation.
FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice, Journal of Clinical Investigation.
FAM83A and FAM83B: candidate oncogenes and TKI resistance mediators, Journal of Clinical Investigation.

Related Stories

PET scan with [11C]erlotinib may provide noninvasive method to identify TKI-responsive lung tumors

July 5, 2011
A non-invasive PET imaging technique may identify lung cancers that respond best to tyrosine kinase inhibitors (TKIs), allowing doctors to better select patients for personalized therapy, according to research presented at ...

Double whammy: RNAi enhances lung cancer therapy

March 20, 2012
Non-small cell lung cancer (NSCLC), the most common form of lung cancer, is usually treated with surgery and chemotherapy. However, a small group of patients can also be helped by treatment with tyrosine kinase inhibitors ...

Computational analysis identifies drugs to treat drug-resistant breast cancer

July 31, 2012
Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results, which are published in Molecular Systems Biology, reveal that the disruption of ...

Recommended for you

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

0 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.