Anticancer drug prevents heart damage from chemotherapy

Australian biotech Race Oncology has found its drug Zantrene is able to protect heart muscle cells from death, while improving the killing of breast cancer cells, when used in combination with the anthracycline known as doxorubicin. This is the first time a drug has demonstrated the ability to both target the cancer and protect the heart from anthracycline damage, offering hope to cancer patients who undergo chemotherapy with anthracyclines and are at risk of serious and permanent damage to their hearts.

Anthracyclines are recognised as some of the most effective anticancer treatments ever developed and are used in more types of cancer than any other class of anticancer agents. However, fears over the damaging side effects of anthracyclines to the heart have led many oncologists to limit their use.

Zantrene (bisantrene dihydrochloride), meanwhile, was originally developed in the 1970s as a heart-safe alternative to anthracyclines before approval in France in the 1990s. While the drug’s improved heart safety was proven in more than 50 clinical trials, the question of whether Zantrene could help prevent the heart damage caused by anthracyclines was never addressed.

The Zantrene heart safety research program is being led by cardiotoxicity researchers Associate Professors Aaron Sverdlov and Doan Ngo, in collaboration with cancer scientist Associate Professor Nikki Verrills, at The University of Newcastle. The team’s preclinical model found that Zantrene protects the heart muscle cells from damage by doxorubicin while synergising with the anthracyclines to better kill breast cancer cells.

“To date, the concept of potential cancer therapies that are not only non-cardiotoxic but, in fact, cardio-protective, has not been evaluated or even entertained, largely due to ‘disease-specific’ approaches in health care,” Assoc Prof Sverdlov noted.

“Our results suggest that Zantrene, an effective anticancer medication, can concomitantly provide protection against toxic effects on the heart from one of the most commonly used chemotherapy agents, doxorubicin. This is the first evidence of its kind to demonstrate that there is a therapy that both targets the cancer and protects the heart. This has the potential to improve health outcomes for countless cancer patients and survivors by both improving their cancer treatment while preventing development of cardiovascular disease.”

Race Oncology’s discovery thus has the potential to revolutionise the use of anthracyclines by allowing oncologists to use these powerful drugs to their full anticancer potential without fear of permanent damage to the heart. The company has submitted a patent application addressing the combination of Zantrene with an anthracycline for the protection of the heart of patients, and advanced discussions are underway with Australian clinicians to run a Phase 2b clinical trial in breast cancer patients at serious risk of anthracycline-induced heart damage. Additional preclinical studies will aim to investigate if Zantrene can protect the heart from damage by other chemotherapeutic drugs which are also known to cause cardio-damage, while further studies will seek to determine the molecular mechanism of Zantrene’s cardio-protective activity.

“To find that Zantrene can protect the heart from chemotherapy while also killing cancers better is an extraordinary ‘best of both worlds’ outcome,” said Dr Daniel Tillett, Chief Scientific Officer at Race Oncology. “Given anthracyclines are used in millions of cancer patients every year, it is hard to overstate the clinical and commercial potential of this breakthrough.”

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

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