Nav: Home

UA Cancer Center team targets tumor suppressor to treat 'triple-negative' breast cancer

February 05, 2018

A study by scientists at the University of Arizona Cancer Center and Cancer Research UK has found that the loss of a specific tumor suppressor in "triple-negative" breast cancer provides clues about potential new approaches to treatment. The results were published on Jan. 30 in the journal Cell Reports.

Triple-negative breast cancers lack three receptors that can be targeted by drugs, which limits treatment options. Therapy can be "targeted" to be more specific to a patient's individual tumor profile, allowing for the delivery of "personalized" medicine. Currently, patients with triple-negative breast cancer are treated with radiation or chemotherapy, and lack options for targeted forms of treatment.

In response, the UA Cancer Center's Agnieszka Witkiewicz, MD, professor of pathology, and Erik Knudsen, PhD, professor of medicine at the UA College of Medicine - Tucson, analyzed unique features of triple-negative breast cancer to identify possible new approaches for treatment. Previous research from the group showed that about 20 to 30 percent of triple-negative breast cancers have lost the retinoblastoma (RB) tumor suppressor. Drs. Witkiewicz and Knudsen hypothesized that loss of this tumor suppressor in the subset of triple-negative breast cancers may provide a target for novel drugs.

A properly functioning RB tumor suppressor is present in normal breast cells and helps to maintain control over cell division. The loss of the RB tumor suppressor impairs one of the body's critical defense mechanisms against cancer formation.

"The lack of a personalized strategy to apply medicine based on specific features of a patient's tumor remains one of the seminal therapeutic challenges in the treatment of triple-negative breast cancer," said Dr. Witkiewicz. "Therefore, exploiting the loss of RB could represent a significant conceptual change in the way we consider treatment."

Three promising candidates emerged from a search for drugs that could target triple-negative breast cancers with the missing RB tumor suppressor. These tumors were susceptible to drugs that target PLK1 and AURK, proteins that are key drivers of cell division, and CHK1, a protein that is important for DNA replication. These proteins can be used as biomarkers, properties of a tumor that can be measured in blood to let doctors know more about a patient's cancer and how best to treat it.

The studies showed that triple-negative breast tumors lacking the RB tumor suppressor harbor increased levels of these biomarkers. Developing drugs that target PLK1, AURK and CHK1 could represent a strategy for treating the 20 to 30 percent of triple-negative breast cancer patients whose tumors do not respond to targeted treatments.

"Drugs that attack PLK1 or CHK1 wreak catastrophic damage on tumor cells that have lost RB," said Dr. Knudsen. "These studies underscore the importance of understanding fundamental features of tumor cell division and delineating how to target tumor-specific vulnerabilities with new drugs to exploit those events therapeutically."

The authors caution that these findings, while provocative, need further exploration. The group is planning studies to investigate PLK1, AURK and CHK1 inhibitors in clinical trials to test the effectiveness of drugs that target RB-deficient triple-negative breast cancer.

"A biomarker-driven clinical trial will be critical in advancing this concept from the laboratory to the clinic," said Dr. Witkiewicz.

Breast cancer is the most common type of cancer in the United States, with an estimated 252,710 diagnoses and 40,610 deaths in 2017, according to the National Cancer Institute. About 10 to 20 percent of breast cancers are triple-negative, and targeted treatments are necessary to decrease mortality associated with this aggressive form of the disease. Beyond triple-negative breast cancer, drugs that target RB-deficient tumors could have implications for other types of cancers in which tumors lose the RB tumor suppressor.
-end-
Other study investigators include: Sejin Chung, BS, and Paris Vail, MS, of the UA Cancer Center, and Chris Lord, PhD, and Rachel Braugh, PhD, of Cancer Research UK.

This research was supported by grants from the National Institutes of Health (under grant Nos. CA188650 and CA163863) and program funding from Breast Cancer Now.

About the University of Arizona Cancer Center

The University of Arizona Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center headquartered in Arizona. The UA Cancer Center is supported by NCI Cancer Center Support Grant No. CA023074. With primary locations at the University of Arizona in Tucson and at Dignity Health St. Joseph's Hospital and Medical Center in Phoenix, the UA Cancer Center has more than a dozen research and education offices throughout the state, with more than 300 physicians and scientists working together to prevent and cure cancer. For more information: uacc.arizona.edu

About the University of Arizona Health Sciences

The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. The UA Health Sciences includes the UA Colleges of Medicine (Phoenix and Tucson), Nursing, Pharmacy and Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the growing Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, the UA Health Sciences reaches across the state of Arizona and the greater Southwest to provide cutting-edge health education, research, patient care and community outreach services. A major economic engine, the UA Health Sciences employs almost 5,000 people, has nearly 1,000 faculty members and garners more than $140 million in research grants and contracts annually. For more information: uahs.arizona.edu

University of Arizona Health Sciences

Related Breast Cancer Articles:

Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
Blood test offers improved breast cancer detection tool to reduce use of breast biopsy
A Clinical Breast Cancer study demonstrates Videssa Breast can inform better next steps after abnormal mammogram results and potentially reduce biopsies up to 67 percent.
Surgery to remove unaffected breast in early breast cancer increases
The proportion of women in the United States undergoing surgery for early-stage breast cancer who have preventive mastectomy to remove the unaffected breast increased significantly in recent years, particularly among younger women, and varied substantially across states.
Breast cancer patients with dense breast tissue more likely to develop contralateral disease
Breast cancer patients with dense breast tissue have almost a two-fold increased risk of developing disease in the contralateral breast, according to new research from The University of Texas MD Anderson Cancer.
Some early breast cancer patients benefit more from breast conservation than from mastectomy
Breast conserving therapy (BCT) is better than mastectomy for patients with some types of early breast cancer, according to results from the largest study to date, presented at ECC2017.
One-third of breast cancer patients not getting appropriate breast imaging follow-up exam
An annual mammogram is recommended after treatment for breast cancer, but nearly one-third of women diagnosed with breast cancer aren't receiving this follow-up exam, according to new findings presented at the 2016 Annual Clinical Congress of the American College of Surgeons.
Low breast density worsens prognosis in breast cancer
Even though dense breast tissue is a risk factor for breast cancer, very low mammographic breast density is associated with a worse prognosis in breast cancer patients.
Is breast conserving therapy or mastectomy better for early breast cancer?
Young women with early breast cancer face a difficult choice about whether to opt for a mastectomy or breast conserving therapy (BCT).
Breast density and outcomes of supplemental breast cancer screening
In a study appearing in the April 26 issue of JAMA, Elizabeth A.
Full dose radiotherapy to whole breast may not be needed in early breast cancer
Five years after breast-conserving surgery, radiotherapy focused around the tumor bed is as good at preventing recurrence as irradiating the whole breast, with fewer side effects, researchers from the UK have found in the large IMPORT LOW trial.

Related Breast 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

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".