Researchers from the University of Florida propose a novel therapy to treat colon cancer. They suggest that a small addition to a cancer drug could possibly make a large difference in treatment. The investigators claim to have discovered a way that uses just a fraction of the normal dosage of a chemotherapy drug to attain improved results against colon cancer cells. The drug is known to be highly toxic and debilitating.
With established human tumors, this new finding in human colon cancer cell lines and mice reveals that the addition of a tiny molecule to the Temozolomide cancer drug could be better for patients with colon cancer. The inclusion of this molecule seemed to disrupt the repair mechanisms in a type of tumor cells that were otherwise known to be highly resistant to treatment.
“This is very important because aside from aggressive surgery with possibly chemotherapy, there are no specific treatments for colon cancer. The recurrence rate for this type of cancer after surgery is very high, about 30 to 50 percent, and there is an urgent need to develop new approaches to manage this deadly disease,†mentioned Satya Narayan, a professor of anatomy and cell biology at the College of Medicine and a member of the UF Shands Cancer Center.
The research team examined over 140,000 small molecules. They finally arrived at a small molecule that appeared to exactly block cancer cells capability to identify and repair the DNA damage inflicted by Temozolomide, or TMZ.
“Our idea was if you induce DNA damage (with TMZ), and at the same time block cell repair, you can synergize toxic effects to the cancer cells,†Narayan commented further. “We hope that with this combination treatment we can reduce the tumors drastically and expand the lifetime of patients much longer than is currently possible.â€
Commonly, TMZ is used against certain types of brain cancer and it functions by damaging the DNA of the cancer. Experts indicate that the challenge of treating patients though was that colon cancer was not a single disease but an array of disorders with unique molecular mechanisms. And one type in particular was found to be quite proficient at repairing the DNA damage inflicted by the drug.
Narayan’s team claimed to have disabled the colon cancer’s ability to manufacture repaired enzymes by combining TMZ with the small molecule. In their analysis of mice with human colon cancer tumors, the investigators utilized an amount of TMZ that was about 10 times lower than recommended.
According to Narayan if just one-tenth as much TMZ is required to kill cancer cells, then possibly use of lower doses of a drug could create large adverse side effects partial listing of which comprised anxiety, back pain, breast pain, constipation, cough, diarrhea, dizziness, drowsiness, dry skin, hair loss, headache, joint pain, loss of appetite, mouth sores, muscle aches and nausea.
“By using these strategies we can predict that disruption of DNA repair by small molecules can bypass drug resistance factors and dramatically reduce side effects caused by toxic doses of TMZ,†Narayan said. “This could be the start of other small molecule inhibitors,†he said.
Narayan believes that additional investigations are required before the combination can be tested in patients. However he is also of the opinion that TMZ could be combined with the small molecule in a single dose in pill or capsule form.
The research will be featured on the cover of December’s Molecular Cancer Research, a journal of the American Association for Cancer Research.