Nav: Home

Mayo Clinic researchers clarify chemo resistance, and perhaps a new therapy

March 09, 2017

ROCHESTER, Minn. -- Mayo Clinic scientists have identified a specific protein implicated in drug resistance, as well as a possible therapeutic tool. Their work appears in the EMBO Journal.

The team led by Haojie Huang, Ph.D., a Mayo Clinic tumor biologist within Mayo Clinic's Center for Biomedical Discovery identified the role of FOXO1 in chemotherapy resistance.

They also identified a potential therapeutic tool by engineering a peptide, which is a short segment of amino acids.

Taxanes: response and resistance

Cancer medications come in many forms. One family of chemicals called taxanes is used to treat advanced cancers. However, over time taxanes can become less effective. Cancer cells reroute communication signals down other pathways. In this study, the authors looked at how this rerouting, or resistance, occurs in relation to the activity of enzymes called kinases.

Kinase ringleaders

Cells need energy to function. Kinase enzymes help by trading chemicals back and forth on specific molecules, often proteins. This activity fuels cellular functions. The authors examined the serine/threonine kinase AKT. AKT's actions generally help cells survive. But when it goes awry, this kinase plays a central role in many types of cancer. Drugs that shut down AKT have great therapeutic promise. But, because of the complexity inherent in cellular communication, those therapies themselves instead may allow cancer to survive.

New mechanism

In this new study researchers treated cancer cells with taxanes, which block, or inhibit, AKT action. They found that taxanes prevent a protein called FOXO1 from migrating out of the cell's nucleus. When FOXO1 stays put in the nucleus, another protein, ERK, becomes inappropriately active and kicks off signals that help cancer survive and develop resistance.

"This is why, despite great therapeutic promise, none of the AKT inhibitors have been approved by the Food and Drug Administration for anticancer use in clinic," explains Dr. Huang.

But, when FOXO1 does migrate out of the nucleus, it attaches to a scaffolding protein called IQGAP1. That binding action blocks the activation ERK and prevents chemotherapy resistance.

"We also found that cotreatment with a taxane and a small FOXO1-derived peptide inhibitor blocks ERK activation and tumor growth," says Dr. Huang. "Uncovering this new and important mechanism of drug resistance may, one day, allow us to develop new therapeutics to overcome the resistance to taxane and AKT inhibitory medicines in cancers which harbor genetic lesions leading to hyper-activation of AKT."

This engineered peptide inhibitor has been patented by Mayo Clinic Ventures, the commercialization arm of Mayo Clinic.
-end-
In addition to Dr. Huang, other authors are:
  • Chun-Wu Pan, Mayo Clinic and Xinhua Hospital Shanghai Jiao Tong University School of Medicine
  • Xin Jin, M.D., Mayo Clinic
  • Yu Zhao, Ph.D., Mayo Clinic
  • Yunqian Pan, Mayo Clinic
  • Jing Yang, Mayo Clinic
  • Jeffrey Karnes, M.D., Mayo Clinic
  • Jun Zhang, M.D., Mayo Clinic
  • Liguo Wang, Ph.D., Mayo Clinic


The authors reported no conflicts of interest. Funding for this work was provided by the National Institutes of health, the U.S. Department of Defense, Mayo Clinic Center for Individualized Medicine and the National Natural Science Foundation of China. Dr. Huang also receives funding from the Center for Biomedical Discovery.

About Mayo Clinic

Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit mayoclinic.org/about-mayo-clinic or newsnetwork.mayoclinic.org.

Mayo Clinic

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".