Particle shows promise for treating the deadliest type of breast cancer

May 18, 2018

USC researchers have pinpointed a remedy to thwart a protein that helps the metastatic spread of breast cancer, a leading cause of death for women. The findings appear today in Nature Communications.

The study comes from the lab of USC stem cell researchers at the Keck School of Medicine of USC and offers a novel solution to suppress cancer from metastasizing into the lungs. It's positive news for patients with triple-negative breast cancer (TNBC) - the deadliest type - that comprises 20 percent of breast cancer cases and is particularly difficult to treat. Researchers are intensely interested in finding new treatments for TNBC.

"For this subtype of breast cancer, few treatment options are available to target metastasis, and typically, these treatments are associated with high toxicity," said Min Yu, an assistant professor of stem cell biology and regenerative medicine, and a principal investigator at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, and the USC Norris Comprehensive Cancer Center. "A better understanding of tumor cells and their interactions with organs and tissues could help us design targeted therapies specific for metastasis."

In Yu's laboratory, postdoc Oihana Iriondo and her colleagues showed that by inhibiting a protein called TAK1, they were able to reduce lung metastases in mice with TNBC. It appears that TAK1 enables malignant cells from the breast to survive in the lungs and form new metastatic tumors. Metastases are the most common cause of cancer-related death.

There's already a potential drug, called 5Z-7-Oxozeaenol or OXO, that can inhibit TAK1--and presumably make it much more difficult for breast cancer cells to form lung metastases. However, OXO is not stable in the blood, and therefore wouldn't work in patients.

To overcome this obstacle, Yu and her lab teamed up with the laboratory of Pin Wang at the USC Viterbi School of Engineering. Wang's team developed a nanoparticle - consisting of a tiny fatty sac - that works like a smart bomb to carry drugs through the bloodstream and deliver them directly to tumors. The scientists loaded this nanoparticle with OXO, and used it to treat mice that had been injected with human breast cancer cells. While OXO did not shrink primary tumors in the breast, it greatly reduced metastatic tumors in the lungs with minimal toxic side effects.

"For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic," Yu said. "So nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis."

Metastatic breast cancer is also classified as Stage 4 breast cancer once it's spread to other parts of the body, usually the lungs, liver or brain. It reaches these organs by penetrating the circulatory or lymph system and migrating through blood vessels, according to the National Breast Cancer Foundation.

Breast cancer is the most common cancer in American women, except for skin cancers, and the average risk of developing breast cancer is 1 in 8 for a woman in the United States, according to the American Cancer Society. About 266,120 new cases of invasive breast cancer are diagnosed in women each year, and about 40,920 women will die from it, the ACS estimates.

The USC research is in early-stage development using animal tests. The method the researchers discovered shows promise, but more research will be needed before it could be applied to humans for treatment.
-end-
Study authors include Oihana Iriondo, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, and Min Yu from the USC Keck School, and Yarong Liu and Pin Wang from USC Viterbi.

Funding came from the National Cancer Institute (K22 CA175228-01A, P2CA206653, and P30CA014089) and the USC Ming Hsieh Institute for Engineering Medicine for Cancer.

USC Stem Cell is a collaborative, multidisciplinary effort working to translate the potential of stem cell research to the clinical imperative of regenerative medicine. Centered at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, the initiative brings together nearly 100 research and clinical faculty members from the Keck School of Medicine of USC, Children's Hospital Los Angeles, the USC Viterbi School of Engineering, the USC Davis School of Gerontology, the Ostrow School of Dentistry of USC, the USC School of Pharmacy, and the USC Dornsife College of Letters, Arts and Sciences.

University of Southern California - Health Sciences

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.