Treating triple negative breast cancer by targeting pair of receptors

March 27, 2018, Baylor College of Medicine
Micrograph showing a lymph node invaded by ductal breast carcinoma, with extension of the tumour beyond the lymph node. Credit: Nephron/Wikipedia

Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks known targets for therapies, making it difficult to treat. However, a new study by a group of researchers and physician-scientists, led by Baylor College of Medicine, has identified a novel treatment strategy that may be effective for TNBC patients. The study appears in Nature Medicine.

Many types of cancers are caused by that promote the growth of cancers. But the receptors driving some cancer types like TNBC have remained elusive to scientists, until now. In the current study, scientists at Baylor have discovered a pair of receptors that cooperate to drive this deadly disease. Therapies inhibiting these receptors in combination can dramatically shrink TNBCs, including those cancers that are resistant to standard chemotherapy.

Previously, this research team had discovered a gene called PTPN12 that prevents TNBC from occurring. PTPN12 is frequently inactivated in TNBC , thus leading to development of the cancer. In the current study, investigators discovered how PTPN12 works to prevent cancer by turning off at least two cancer-promoting receptors. When PTPN12 is inactivated, these receptors become stuck in the "on position" and drive the cancer to grow. This finding led investigators to test the idea that inhibiting both of these key receptors in combination could kill TNBCs.

"This study could have a major impact on our understanding and treatment of triple negative breast cancer, and has prompted two clinical trials," said Dr. Trey Westbrook, director of the Therapeutic Innovation Center at Baylor and McNair Scholar of cancer research. "The first trial testing the effect of inhibiting these receptors was unsuccessful because the two drugs, when used together, were not tolerated by patients. However, a new, single drug has been developed that hits the right combination of receptors, but has much fewer off-targets and side effects, meaning the drug is far more precise in inhibiting these cancer-causing receptors while sparing normal tissues."

To test the efficacy of inhibiting these receptors in TNBCs, tumors from 14 different patients were grown in mice. While these cancers did not respond to standard chemotherapy, many of them shrank in response to this new therapeutic strategy.

"In TNBCs from half of the patients, we saw tumor regression. This finding could have major clinical implications," said Westbrook, who also is a professor of molecular and human genetics and biochemistry and molecular biology at Baylor. "These results provide a molecular mechanism to match this new therapeutic approach with patients most likely to respond."

The Lester and Sue Smith Breast Center, part of the Dan L Duncan Comprehensive Cancer Center at Baylor, is working through the approval processes to begin enrolling TNBC patients in a clinical trial to test this therapeutic strategy.

"This groundbreaking work offers the most promising prospect of targeted therapy for triple negative . We are very excited about exploring this promise in patients with our planned clinical trial," said Dr. Mothaffar Rimawi, associate professor, medical director and clinical research director in the Lester and Sue Smith Breast Center at Baylor.

Dr. Matthew Ellis, professor and director of the Lester and Sue Smith Breast Center and McNair Scholar at Baylor said, "While various approaches to categorizing TNBC have been published, the only ones that matter are those that have the potential to drive therapeutic decisions. This work further solidifies the hypothesis that despite the TNBC label, a substantial number of these aggressive tumors have activated receptor kinases that can be successfully targeted."

In the future, the research team is hopeful that this same therapeutic approach can be applied to many different types of cancers.

Explore further: Researchers identify potential therapeutic target in aggressive breast cancer cells

More information: Amritha Nair et al. Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer, Nature Medicine (2018). DOI: 10.1038/nm.4507

Related Stories

Researchers identify potential therapeutic target in aggressive breast cancer cells

November 15, 2017
An especially aggressive breast cancer cell can respond to hormone therapy if they express a specific protein known as estrogen receptor beta (ERβ), according to new research published on the cover of Oncotarget. The findings ...

Study identifies potential targets for treating triple negative breast cancer

August 29, 2016
No specific treatments are currently available for triple negative breast cancer (TNBC), a type of tumor that lacks the receptors targeted by many breast cancer therapies. Although many TNBC tumors lack two tumor suppressors, ...

Researchers identify novel treatment for aggressive form of breast cancer

May 23, 2016
A recent study by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine revealed that triple-negative breast cancer (TNBC), which has generally been unresponsive to hormone ...

Study uncovers therapeutic targets for aggressive triple-negative breast cancers

February 3, 2018
As part of a breast-cancer diagnosis, doctors analyze the tumor to determine which therapies might best attack the malignancy. But for patients whose cancer is triple-negative—that is, lacking receptors for estrogen, progesterone ...

HRD-positive breast cancer patients fare better with adjuvant AC chemotherapy

March 19, 2018
People with tough-to-treat triple negative breast cancer, whose tumors also don't allow for double-strand DNA repair, fare better when treated with a common adjuvant breast cancer chemotherapy combination, according to results ...

Novel molecular pathway in aggressive breast cancer offers potential therapeutic targets

April 21, 2017
University of Tsukuba-led researchers identified a novel molecular mechanism involved in progression and metastasis in the most aggressive form of breast cancer. The gene MAFK is known to be induced by the TGF-β signaling ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...


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.