Smartbomb: A Hope for Destroying Cancer Tumors

When I first heard I had cancer, I had to take sleeping pills at night because I couldn’t sleep without thinking about it. For the first two weeks, I would wake up, forget and then remember what was happening. I cried every day,” said Brenda Haley, of Ulman, MO. “I honestly thought I was going to die. I hate cancer! It is scary." 

Haley was diagnosed in  fall of 2011 with cervical cancer. "I couldn’t see it and because it was in its early stages, I couldn’t feel it," stated Haley. "Now that I have gone through treatment, I am more tired than I’ve been in my life. I feel nauseous constantly, and I burn when I use the restroom. I am also very emotional. My body feels like it’s betraying me, and sometimes I feel like I can’t do this anymore. Gradually, I have accepted what is happening to my body and deal with it better when I wake up.”

This disease has affected not only her, but everyone around her. As her daughter, it is terrible seeing her go through this. That is why new cancer researcher are using “smartbombs” in the hope that one day, people won’t have to go through times like that.

According to a 2009 article on the CBS Evening News Website, more than 14,000 women are diagnosed with cervical cancer each year, resulting in up to 3,900 deaths. There are treatments for this disease , depending on what stage the cancer is in, which means its size, depth of invasion, and how far it has spread. There are three main methods of cancer treatment: surgery, radiation, and chemotherapy. (Haley was treated with all three.)  During and after treatments of radiation/chemotherapy, there are many side effects , such as tiredness, nausea, loose bowels, low blood counts, and the skin in the treated area feeling/looking almost sunburned, according to the American Cancer Society.

On September 12, 2011, the British Science Festival, organized by the British Science Association, was held in Bradford, England as a scientific outreach event.  There, a group of scientists from the University of Bradford informed the public about a "chemotherapy breakthrough" using a chemical derived from colchicine found in crocuses.  They claimed it was a ‘new drug’ that could "bring hope to millions, dramatically reduce side-effects and kill tumors in one treatment." They called it a "smartbomb".

Colchicine, derived from the autumn crocus plant, was originally used to treat patients with gout. In 2009, the Food and Drug Administration (FDA) approved colchicine as a therapy for two illnesses (familial Mediterranean fever and acute gout flares). Although colchicine has medicinal properties, it is extremely toxic and has been compared to arsenic poisoning.

Colchicine has been investigated as an anti-cancer agent and has proven to be effective in treating cancerous cells. Colchicine brutally damages a cell’s inner layers by blocking the action of a protein called tubulin. Tubulin plays an important role as cells divide into two.  Thus, colchicine effectively halts cell division. Stopping cell division is a vital part of potential cancer drugs. Unfortunately, colchicine attacks not only cancer cells, but healthy ones as well, classifying it as a poison.

Laurence Patterson, Professor of Drug Discovery and Institute Director of The Institute of Cancer Therapeutics at the University of Bradford, and his research team are trying to tweak the molecule to make it less toxic, making it more suitable to investigate as an anti-cancer drug. Patterson and his team’s strategy would deliver the colchicine directly to the tumor, which would isolate it from the rest of the body, according to Patterson’s research paper published by the American Association for Cancer Research. Most chemotherapy, the treatment most often used to treat cancer, is also toxic to healthy cells. However, scientists have not been able to target the chemotherapy at specific cells.

To ensure that the colchicine directly targets the tumor, the researchers enlisted a family of proteins called matrix metalloproteases (MMPs) for help. MMPs, extremely powerful enzymes, are produced in large amounts in many cancers. These enzymes can dissolve the material known as the extracellular matrix around cells. Cancer cells use these MMPs to get access to new blood vessels, providing necessary oxygen and nutrients, according to the Cancer and Metastasis Review by Elena I. Deryugina and James P. Quigley.

The Bradford researchers attach long molecular "tails" to single colchicine molecules. This customized colchicine (ICT2588) is nontoxic until it comes into contact with MMP1, a metalloprotease protein released by tumors. 

"Our novel delivery system uses the presence of this active MMP to activate the drug, which attacks and breaks down cancer blood vessels, destroying the tumor's lifeline," explained Patterson. "What is also novel about our approach is that we are effectively targeting the blood supply of the tumor. If you can starve the tumor of that blood supply, then you can cut off its ability to grow and to move around the body."

That is the researchers’ theory. So far, they have tested customized colchicine in mice carrying a variety of human tumors, including breast, colon, sarcoma, prostate and lung cancers. After two months of trials, half the mice studied were declared cancer-free with just a single dose. The scientists hope to start human trials in 18–24 months.

Curing human cancers may still be slightly out of reach, but this research gives cancer patients and their families, including my family, the hope they need in this difficult time. Kori Haley

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