Botox Could Help Target Resistant Tumors for Treatment

The cosmetic treatment Botox may have a new use as an adjuvant to cancer therapy, providing an open door for chemotherapy and radiation treatments, according to a study published in the Feb. 15 issue of Clinical Cancer Research.

The study in mice, led by Bernard Gallez, Ph.D., professor of pharmacy at the Universite' de Louvain in Brussels, Belgium, found that by injecting Botulinum neurotoxin type A into two types of mouse tumors, the tumors' cellular vasculature opened, allowing for more effective destruction of previously resistant cancer cells. The study is the first to test the idea of using Botox against cancer and explores the possibility of its use as an adjuvant, assisting the effective delivery of chemotherapies and radiation.

The findings mark a relatively new area of cancer research, which focuses on briefly opening blood vessels that feed tumor cells in order to better deliver therapeutic agents. Until recently, much cancer research has focused on the opposite: reduction of blood vessel growth, which starves tumor cells of nutrients.

"Tumor vasculature is targeted by several advanced anti-cancer approaches that may appear contradictory," said Gallez. "Anti-angiogenesis and anti-vascular targeting are methods aimed at destroying the vessels that feed tumors, thereby depriving them of oxygen and nutrients.

"In contrast, pro-vascular approaches increase tumor perfusion and oxygenation temporarily."

While chemotherapy and radiation treatments have remained the standard of care, tumor cells of most cancer types have shown increasing resistance to therapies. This phenomenon has resulted in more toxic dosages of chemotherapy and radiation, and increased efforts to develop more drugs to which tumors don't show resistance. To increase the efficacy of anti-cancer treatments, the new study examined strategies that transiently opened the tumor vascular bed to alleviate tumor hypoxia.

"Hypoxia is a source of resistance to radiotherapy, and is a determining factor in the poor prognosis of tumors to cytotoxic treatments," said Gallez. "Botulinum toxin could lead to inhibition of contractions of tumor vessels, improve tumor perfusion and oxygenation, and enhance the response of tumors to radio- and chemotherapy."

Botulinum toxin is a naturally occurring molecule, and historically has been implicated with intestinal poisonings. It has been developed for several clinical applications, including facial spasms, strabismus (a disease of the eye muscles), and other muscle hyperactivity. It also has become popularly known as Botox for its cosmetic uses on the face.

The toxin acts on the nervous system by blocking the release of neurotransmitters, particularly acetylcholine and norepinephrine. Gallez and his colleagues hypothesized that since Botulinum toxin impeded neurotransmitter release in the sympathetic nervous system, it could prevent neuromuscular contractions of vessels in tumors. The inhibition of this contraction could literally open the gate to improved tumor perfusion by chemotherapeutic drugs and oxygenation that enhances radiotherapy.