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Understanding Prostate Cancer

Can Botox Tame Prostate Cancer?

April 26, 2013 -- Mention Botox and aging Hollywood stars come to mind. The drug, formally known as Botulinum toxin type A, is widely used to erase wrinkles around the eyes and forehead when it’s injected under the skin. It works, in part, as a nerve blocker. It is also used to treat certain neurological medical conditions. But can Botox work against cancer cells? That tantalizing question is being explored in first-of-kind work by Prostate Cancer Foundation Funded-Researcher Gustavo Ayala, MD and colleagues at the University of Texas Health Science Center, in Houston.

Much study has been devoted to demonstrating the importance of blood vessel support to cancer growth and progression, especially in what is known as the tumor microenvironment. Tumors must have a robust knot of blood vessels to support their greedy need for oxygen and nutrients. This extra-rich supply of blood vessels forms part of the microenvironment that supports tumor growth, and drugs and research abound to interfere with blood supply to tumors. There are several FDA-approved anti-cancer drugs that block new blood vessel formation, such as the angiogenesis inhibitor Avastin® that is used to treat a variety of cancers.

Yet, comparably, almost no attention has been paid to what role nerves play in cancer growth and progression. Dr. Gustavo Ayala has established himself as the leader in this latter area of cancer research, and his laboratory’s focus on how cancers can induce new nerve growth (neurogenesis) in order to thrive inside a patient is unique in this nation. His group also focuses on the effects of tumor denervation, primarily through the use of the neurotoxin Botox. Just like anti-angiogenesis drugs inhibit blood vessel growth in order to starve tumors, Ayala is working out if Botox can starve tumors of the innervation they need to thrive and grow in patient’s bodies.

Botox shriveled tumor cells in men prior to surgery; injections of the drug into tumor may enhance effects of radiation therapy.

Ayala is the first to describe cancer-induced neurogenesis and show that as prostate cancer cells invade local nerves, the cancer cells spur new nerve formation, which can lead to the spread of cancer cells from their site of origin. His data has also demonstrated that when prostate cancer cells invade the protective sheath covering local nerves, a process he’s dubbed perineural invasion, or PNI, those cancer cells are far less likely to be killed by radiation therapies used to eradicate cancer cells from the prostate gland. Ayala likens this to prostate cancer cells taking refuge in a bunker during the “war” of radiation therapy, only to emerge stronger and more likely to live on to fight another day, to the detriment of the patient.

In his exploration of whether Botox can disrupt cancer-induced new nerve growth and slow cancer progression, Ayala opened a clinical trial at two Houston hospitals. Men in the study had bilateral prostate cancer; each side of their prostate gland was injected—one side with plain saline solution, the other with the neurotoxin Botox. Four weeks later, the men underwent prostatectomy to remove their Gleason 6-7 tumors at which time tissue from each side of their prostate gland was examined for signs of tumor death.

The early results of this trial (Phase I) showed that on the side of the prostate injected with Botox, the tumor cells shriveled compared to the side injected with saline. No significant effect on blood vessel formation was seen, suggesting that the cellular degeneration was due to the neurotoxic effects of Botox rather than any collateral anti-angiogenesis effect from the drug.

Going forward, Ayala will also examine potential therapeutic windows in order to determine the best time to use Botox to kill nerves in the prostate. This may include men undergoing active surveillance or those who opt for radiation therapy.

Ayala has almost singlehandedly opened the door to understanding how nerves and neurogenesis can initiate and spread prostate cancer. To date, he has shown that using Botox to cut nerves in cancers may enhance the effects of radiation therapy and can decrease tumor formation in lab animals.

And by targeting the nerves that may be supporting their cancers, he hopes his clinical trials will bring about positive clinical outcomes for men with prostate cancer.

Dr. Ayala is the recipient of the Gordon Becker – PCF Creativity Award

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