Targeting tumors with toxins
Arsenic is a naturally occurring toxin found in groundwater that is absorbed into what we eat and drink – including foods such as rice and apple juice – and New Mexico has some of the highest concentrations of the metallic mineral in the U.S.
It’s considered a co-carcinogen, because it promotes the activity of other cancer-causing agents. Despite this, UNM researcher Jim Liu, PhD, thinks arsenic has potential as an anti-cancer treatment.
Liu, associate dean for research and professor of pharmaceutical sciences in the UNM College of Pharmacy, started out wondering about arsenic’s cancer-promoting properties. He teamed-up with fellow faculty member Laurie Hudson, PhD to establish that at environmental doses arsenic is a more potent co-carcinogen than a carcinogen by itself.
It turns out that arsenic helps drive cancer development when ultraviolet radiation is absorbed through the skin via exposure to sunlight. So when someone who has ingested arsenic receives a lot of UV radiation (as is often the case in New Mexico), their cells may suffer DNA damage, triggering cancer.
In effect, Liu says, arsenic has a synergistic effect, amplifying the likelihood of carcinogenesis compared to when UV radiation acts alone.
But there’s a bright spot in this picture.
“We have a protection system,” Liu says. “Not everyone gets cancer.” Cells have mechanisms to repair damaged DNA and block the development of tumors. So Liu and Hudson decided to figure out how arsenic interferes with that DNA repair process.
They found that arsenic replaces zinc in a DNA-repairing protein known as poly[ADP-ribose] polymerase 1, hampering its efficacy. This allows UV-induced DNA damage to accumulate in the tissue, increasing cancer risk.
But this process can be flipped around to attack tumor cells in patients undergoing radiation treatment for their cancers.
Radiation therapy often fails when tumor cells resist the treatment by repairing their own DNA, allowing them to survive. According to researchers at the Department of Physics at Oslo University, 80 percent of cancer cell lines assessed in laboratories are sensitive to radiation therapy, but the remainder resist the treatment.
Liu and Hudson reasoned that if they could deliver arsenic to tumor cells being targeted with radiation their DNA repair mechanisms would fail, leading to increased tumor cell death.
“Radiation combined with arsenic is localized into one area,” Liu explains. “Arsenic is all through the body, but effective in one area.”
Liu’s studies show the combined therapy may shrink tumors more effectively than radiation alone and eventually eliminate cancer. Meanwhile, the remaining arsenic in the body is eliminated through the urine in a few days following injection.
Figuring out how to enlist a potential harmful substance like arsenic for use as an anti-cancer treatment is part of the scientific process. Liu smiles: “Everything you do leads to something more interesting.”