Cancer Cell Suicide

Researchers at the University of New South Wales (UNSW) in Australia have developed a new drug that may be a cancer cure-all. The drug, called TR100, works by attacking the proteins that form the structure of cancer cells, while leaving healthy cells alone. Their study, which involved tests on lab rats, was published this month in Cancer Research.

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Like a building, cells need support structures in order to hold their shape. Two proteins called actin and myosin give cancer cells their structure; they are like long, tough, interlocking cables.

Healthy human muscle cells, including the cells that form the heart, also employ actin and myosin. For this reason, most researchers had abandoned actin and myosin as targets for chemotherapy, and the development of drugs targeting these proteins stalled for nearly 25 years.

But world myosin specialist Dr. Peter Gunning pressed on, and now his work has yielded results. He and other researchers were able to isolate two specific types of myosin, called tropomyosins, which cancer cells use but healthy muscle cells don’t. He worked with Dr. Justine Stehn, the paper’s lead author, to develop TR100.

Programmed Cell Death: Making Tumors Implode

"We've really gone after the core component of the internal scaffold or structure of the cancer cell,” said Stehn, a research fellow in the Oncology Research Unit at the UNSW School of Medical Sciences, in an interview with Healthline. "[When] the cell senses that there's something fundamentally wrong with its architecture, it will undergo programmed cell death."

Programmed cell death is a genetic time bomb lurking inside each cell in the human body. If a cell is damaged, infected, or otherwise no longer working properly, the body can signal it to self-destruct. "It's like when you see a building collapse,” said Stehn. “If you take out the structure and the scaffolds, the building will fall in on itself." 

Programmed death causes the cell to break itself down into tidy little packets of material that other cells can absorb, recycle, and reuse.

TR100 appears to trigger this progress in cancer cells by destroying the two tropomyosins that cancer uses. However, stem cells also rely on this form of tropomyosin. Stem cells are active in a developing embryo, generating all of the new cells that will eventually form a healthy baby.

“When a cell is proliferating or growing, tropomyosin is really important,” said Stehn. “When a cell differentiates and becomes a heart cell, a lung cell, or a brain cell, it's no longer growing, and the role of tropomyosin changes and targeting it with [TR100] is no longer toxic."

Human Trials Slated for 2015

This means that TR100 could also affect parts of the human body where stem cells are still active after birth. Stem cells are active in bone marrow where they produce new red blood cells, in the brain where they produce nerve cells to form new memories, and elsewhere.

Stehn tested the drug on heart cells, liver cells, and brain cells in the lab, and all were unharmed.

Stehn then tested TR100 on two types of cancer, neuroblastoma and melanoma, and in both cases, the TR100 killed the cancerous cells while leaving healthy cells alone. She’s confident that it should work on other types of cancer, too. “What we've found is that every tumor cell we've looked at relies heavily on this tropomyosin,” she said. “We haven't found a tumor cell that doesn't express the tropomyosin proteins we target.”

Her research was made possible by The Kids’ Cancer Project, which was willing to fund a study into a technique that the research community had abandoned as a hopeless cause. "Our priority is focused on children's cancer,” Stehn said. “We have developed these compounds with the intent of treating hard-to-treat childhood cancers, like neuroblastoma."

Pictured above is two-year-old Zoe Emin and her mother Alison Emin. The Emins took a trip to visit Peter Gunning and Justine Stehn at UNSW. Zoe is currently in remission from neuroblastoma, a hard-to-treat pediatric brain cancer.

Stehn’s new drug, which will hopefully begin clinical trials in 2015, could help save the lives of children like Zoe. For now, she will be working with Dr. Timothy Cripe at the Nationwide Children’s Hospital as he fine-tunes the drug.

“We know that it's not a silver bullet; it's going to be used in combination with other therapies in the clinic,” Stehn said. "This is a major step forward and provides, for the first time, a new class of anti-cancer drug which can be used in the war against cancer."

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