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Improving the treatment of triple negative breast cancer

A combination of drugs already approved for other types of cancer appears to provide effective treatment for particularly difficult-to-treat forms of breast cancer.

In a new study involving experts from Louisiana State University, a total of 133 drugs already approved by the FDA in the United States, including the drugs ceritinib and , were evaluated using a mouse model and tissues from women with triple-negative breast cancer enzalutamide.

The results were published in the English-language journal "Molecular Cancer".

Risk of triple negative breast cancer

Triple negative breast cancer often affects younger women. Women of African and Hispanic descent and women with deleterious germline mutations in breast cancer susceptibility genes are also more likely to develop this form of cancer, the researchers explain.

This aggressive type of breast cancer accounts for 15-20% of all breast cancers.

What is ceritinib?

According to the team, the drug ceritinib is a so-called small molecule tyrosine kinase inhibitor. Ceritinib is typically used to treat people with non-small cell lung cancer.

What is enzalutamide?

Enzalutamide, on the other hand, is a low molecular weight drug that targets the androgen receptor and is used to treat prostate cancer, the researchers explain.

Combination treatment for triple negative breast cancer

When the two drugs are combined, it appears to be effective in treating drug-resistant triple-negative breast cancer. This form of cancer lacks estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2).

Androgen receptors as a target for cancer therapy

A subtype of this cancer, which represents 12 to 55% of triple negative breast cancers, has androgen receptors (AR). Because androgen receptors stimulate tumor cell progression in estrogen receptor-negative breast cancer, they represent a target in the treatment of triple-negative breast cancer, the team said.

Many affected women are resistant to paclitaxel

One problem with treating triple-negative breast cancer, experts say, is that a significant number of affected women develop resistance to paclitaxel.

Paclitaxel is an FDA-approved drug as a chemotherapy drug for triple-negative breast cancer. New therapeutic approaches are therefore needed. The FDA is the United States Food and Drug Administration.

What did the combined treatment achieve?

Researchers eventually found in their study that ceritinib effectively inhibits the growth of triple-negative breast cancer cells with androgen receptors. To improve drug response, they also chose enzalutamide, an androgen receptor antagonist.

"We have developed a new strategy of combining enzalutamide and ceritinib for the treatment of AR+ TNBC tumors by the dual blockade of androgen-dependent and androgen-independent AR signaling pathways", explains the author of the study, the Dr. Suresh Alahari in a press release.

Inhibited growth of AR+ TNBC cells

A combination of ceritinib and enzalutamide has been shown to produce a robust inhibitory effect on the growth of AR+ TNBC cells. A combination of paclitaxel and ceritinib has also been studied and found to have beneficial effects.

"The combination of paclitaxel and ceritinib showed dramatic inhibition of tumor growth compared to either agent alone. All agents used in our study are FDA cleared, so the combination therapy proposed is likely to be used clinically as well,” Dr. Alahari added.

Author and source information

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This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.

Sources:

Shengli Dong, Hassan Yousefi, Isabella Van Savage, Samuel C Okpechi, Maryl K Wright, et al. : Ceritinib is a new triple-negative therapeutic agent for breast cancer; in: Molecular Cancer (published 06/29/2022), Molecular CancerLouisiana State University Health Sciences Center: LSU Health Research Suggests Novel Combination Therapy for Triple-Negative Breast Cancer (published 06/29/2022), Louisiana State University Health Sciences Center

Important note:
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.