Trial to test new aggressive breast cancer strategy to start soon

Trial to test new aggressive breast cancer strategy to start soon

Researchers are recruiting volunteers for a clinical trial that will use a new therapy to target a “defense switch” on cancer cells that alerts cancer to the threat of chemotherapy.

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

The trial begins in August and is 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 throughout the body and coming back within five years than other breast cancers,” Chaffer said.

“In preclinical studies, we found that an experimental drug, seviteronel, in combination with chemotherapy, could be twice as effective at reducing tumor size than chemotherapy alone,” Chaffer said.

Androgen hormones tell triple-negative breast cancers to adapt to chemotherapy and behave aggressively. Seviteronel works by blocking these warning signs and potentially making other treatments more effective.

dr. Dear said, “This is a great 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 trial is successful, a larger safety study will follow within a year.

The research that led to the trial was supported by the NELUNE Foundation, which awarded Chaffer the Rebecca Wilson Fellowship in Cancer Research in 2017, allowing her to bring her research back to Sydney from the US. The Fellowship is an enduring legacy of sportswriter the late Rebecca Wilson.

New approach for triple-negative breast cancer

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

Research by Chaffer’s team revealed that triple negative cancer cells “switch” their cell status in response to chemotherapy, which not only makes the cancer cells more aggressive but also allows them to evade treatment.

“We found that chemotherapy causes a cell change in cancer cells, which allows them to build up a defense against the chemotherapy. This means that after the treatment, a different type of cancer cell develops, which has become resistant to the chemotherapy and is a major cause of cancer relapse Chaffer explained.

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

dr. Beatriz Perez San Juan, the postdoctoral researcher in associate professor Chaffer’s lab who led the preclinical study, found that activation of androgen receptors in breast cancer cells causes cell state switching. 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 along with seviteronel, an experimental treatment that blocks androgen production. The combination approach produced 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 the cancer throughout the body.

Repurposing an experimental treatment

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

“Our research has shown that seviteronel may be much more beneficial as an adjunct therapy. We found that androgen inhibition blocks the switching between cancer cells, ‘locking’ cancer cells into a chemotherapy-sensitive state. This is why in our preclinical studies, chemotherapy plus seviteronel treatment was more effective than chemotherapy alone in fighting cancer,” said Perez San Juan.

“We hope that this new approach to combination treatment will dramatically reduce drug resistance to improve the effectiveness of standard-treatment chemotherapy and ultimately improve outcomes for patients.”

Those interested in registering interest in the 4CAST clinical trial may contact the St Vincent’s Hospital Sydney Research Office, SVHS.cancerresearch@svha.org.au

Image credit: ©stock.adobe.com/au/crevis

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