Try new strategy for aggressive breast cancer to get started soon

Researchers are recruiting volunteers for a clinical trial that will use a new therapy to target a ‘defense switch’ to cancer cells that warns cancer against the threat of chemotherapy.

The new strategy hopes to improve survival rates for patients with triple negative breast cancer – a treatment-resistant form of cancer that can quickly adapt to chemotherapy – affecting over 1,500 women each year in New South Wales.

Set to begin in August, the trial will be led by Associate Professor Christine Chaffer and Dr Beatriz San Juan of the Garvan Institute of Medical Research, and Senior Staff Specialist in Medical Oncology Dr Rachel Dear of St Vincent’s Hospital Sydney. It will be performed at The Kinghorn Cancer Center in Darlinghurst.

“Triple negative breast cancer is an aggressive disease with a greater chance of spreading around the body and recurring within five years than other breast cancers,” Chaffer said.

“In preclinical studies, we found that an experimental drug, seviteronel, combined with chemotherapy, could be twice as effective in reducing the size of tumors as chemotherapy alone,” Chaffer said.

Androgen hormones tell triple negative breast cancer to adapt to chemotherapy and behave aggressively. Seviteronel works by blocking these warning signals and enabling other treatments to be effective.

Dr Dear said: “This is an exciting opportunity to test a new treatment option for metastatic triple negative breast cancer, for which there is currently a gap in effective drug treatments.”

Seviteronel is not currently approved for clinical use. If this test is successful, it will be followed within a year by a larger safety study.

The research leading to the trial was supported by the NELUNE Foundation, which awarded Chaffer with the Rebecca Wilson Fellowship in Cancer Research in 2017, allowing her to return her research to Sydney from the US. The Fellowship is a lasting legacy for sports journalist the late Rebecca Wilson.

New approach to triple negative breast cancer

About 10-15% of breast cancer cases are diagnosed as triple negative breast cancer, which means the cancer cells lack all three receptors that doctors can target with cancer treatment drugs. Because there are currently no effective targeted therapies, triple negative breast cancers have a poor prognosis compared to other forms of breast cancer.

Research by Chaffer’s team found that triple negative cancer cells ‘change’ their cell status in response to chemotherapy, which not only makes the cancer cells more aggressive but also enables them to escape treatment.

“We found that chemotherapy triggers a cell change in cancer cells that enables them to build a defense against the chemotherapy. This means that after treatment another type of cancer cell develops, which has become resistant to the chemotherapy and a major cause is from cancer relapse, “Chaffer said.

“We aim to put an end to this cancer resistance strategy to improve the effectiveness of chemotherapy for triple negative breast tumors.”

Dr. Beatriz Perez San Juan, the postdoctoral researcher in the laboratory of Associate Professor Chaffer, who is leading the preclinical study, discovered that activation of androgen receptors in breast cancer cells triggers cell status change. Androgens are often thought of as male sex hormones, but are also found at lower levels in women.

In preclinical models of triple negative breast cancer, the researchers administered chemotherapy together with seviteronel, an experimental treatment that blocks the production of androgen. The combination approach causes a 70% to 100% greater reduction in tumor size, compared to chemotherapy alone. This strategy prevented the emergence of chemotherapy-resistant cells and reduced the spread of cancer around the body.

Repurposing in experimental treatment

Seviteronel was originally developed as a standalone therapy for breast and prostate cancers carrying the androgen receptor and has been shown to be safe for patients in phase II clinical trials.

“Our research found that seviteronel may be much more beneficial than adjunctive therapy. We found that androgen inhibition blocks the switching of cancer cell status, ‘locking’ cancer cells into a chemotherapy-sensitive state. This is why chemotherapy plus seviteronel- treatment was more effective then chemotherapy only to target cancer in our preclinical studies, “said Perez San Juan.

“We hope this new combination therapy approach will drastically reduce drug resistance to improve the effectiveness of standard-of-care chemotherapy and, ultimately, improve outcomes for patients.”

Anyone interested in registering interest in 4CAST’s clinical trial can contact St Vincent’s Hospital Sydney Research Office,

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Try new strategy for aggressive breast cancer to get started soon

Source link Try new strategy for aggressive breast cancer to get started soon

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