Chemotherapy hope for hard-to-treat childhood cancers

A whole new class of drugs has been developed that targets the structure of the cancer cell for the first time. The therapy has been proven effective in animal models of neuroblastoma, a cancer that affects children, and melanoma.

“It is much like what happens when you see a building collapse on the TV news,” said the lead author, Peter Gunning, PhD, of the University of New South Wales in Sydney, Australia. “Our drug causes the structure of the cancer cell to collapse—and it happens relatively quickly. We've been surprised and excited by the potential of this treatment.”

The drug may be effective against every type of cancer cell, and the work could lead to an entirely new type of chemotherapy. This could have more positive outcomes for hard-to-treat cancers and have fewer long-term side effects for survivors.

Previous attempts in attacking the architecture of cancer cells have failed because that architecture is shared with the heart and muscle, and so the toxicity was unacceptable. Because earlier research in this area had stumbled due to toxicity, financial support for the research was challenging. Gunning said the research became possible because of The Kids' Cancer Project.

This study, published in Cancer Research (2013; doi: 10.1158/0008-5472.CAN-12-4501), found that disrupting the actin cytoskeleton of tumor cells can be done by targeting isoforms of tropomyosin that are selectively upregulated in cancers. Tropomyosin is a core component of actin filaments. The novel class of antitropomyosin compounds preferentially disrupts the actin cytoskeleton of tumor cells. This impairs both tumor cell motility and viability.

Cardiac structure and function were not adversely impacted by the lead antitropomyosin compound, which is known as TR100. The first clinical trials are expected in 2015, and the CEO of the Kids' Cancer Project is determined to see clinical trials in children with hard-to-treat neuroblastoma.

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