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New Discovery by USciences Researchers Moves Closer to Triple Negative Breast Cancer Treatment

By Brian Kirschner

TNBC Image
Left panel shows TNBC cells (green) grown side by side with normal mammary cells (red) in a mixed co-culture. Right panel demonstrates that following the treatment of the mixed co-culture, our small molecule prefers killing TNBC (dead rounded green) while completely sparing neighboring normal mammary cells (healthy flat red). Empty white arrows point toward dead rounded TNBC cells.

A promising new discovery by University of the Sciences researchers has shown early success in targeting one of the deadliest forms of breast cancer—triple negative breast cancer (TNBC).

Professor of pharmaceutical sciences  Adeboye Adejare, PhD, and associate professor of pharmaceutical science Isabelle Mercier, PhD, along with Zeynep Ates-Alagoz, PhD, who is a professor of pharmaceutical chemistry at Ankara University (Turkey), have discovered a small molecule that exhibits selectivity toward TNBC cells while sparing normal surrounding cells.

Studies have shown that TNBC disproportionately impacts African American, Hispanic, and younger women and can be a worst-case scenario for those with the diagnosis. In women with TNBC, the cancer cells lack receptors for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2), hence the triple negative designation.

Current successful treatment therapies for other breast cancers can use drugs such as tamoxifen and Herceptin® that can target at least one of the receptors. Since TNBC lacks all three receptors, treatment options for women become limited and include high doses of chemotherapy, which have severe side effects and toxicity not only to the TNBC cells but to healthy cells in surrounding tissue. For example, the use of doxorubicin is very cardio toxic; the TNBC may be regressed, but the patient could develop heart failure.

Isabelle Mercier
Isabelle Mercier, PhD 

“The research in the field now is to find more selective therapy that is not extremely toxic,” said Dr. Mercier. “In the modeling and in vitro studies, our compound kills TNBC cells very efficiently. And when mixed with normal cells, it only targets the TNBC ones while keeping the normal surrounding cells healthy and alive.”

With current chemotherapeutic treatments for TNBC, suboptimal doses are given to the patient to not only lessen side effects but to also lower the risk of actually killing the patient due to the drugs’ poisonous nature.

“By selectively killing TNBC cells and sparing normal cells, this small molecule could be delivered in high amounts to patients, if necessary, thus attacking resilient TNBC cells, preventing recurrence, and maintaining quality of life through fewer unwanted side effects,” Dr. Mercier said.

Adeboye Adejare
Adeboye Adejare, PhD 

“As an added benefit, this molecule is very cheap to make,” said Dr. Adejare, whose modification to an existing compound already in public space led to the molecule taking on a targeted property.

“Drug companies are certainly interested in a molecule that exhibits selectivity for TNBC, although there is additional research to be completed,” explained Drs. Adejare and Mercier, who are beginning discussions with grantors and potential licensees to complete the preclinical studies. “We are looking for help in moving the research forward so as to reach clinical trials. We are also moving ahead with additional studies looking for other molecules that can act as adjuvant therapy in the treatment of TNBC.”

The researchers envision moving to clinical trials within the next two years—and if the research continues to progress, to providing a much-needed novel, cost-effective, and lifesaving treatment for TNBC patients, thus moving one step closer to beating this deadly disease.

"In the modeling and in vitro studies, our compound kills TNBC cells very efficiently."

-- Isabelle Mercier, PhD

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