Spotlight

Undoing the Damage Caused by Smoking

Balansky et al., pp. 1047–1054

Smoking causes lung cancer, and quitting smoking (or avoiding cigarette smoke) reduces one's risk of cancer. Still, lung cancer frequently occurs in ex-smokers. Balansky et al. investigated whether drugs could be used to help prevent smoke-related cancers. They found that certain drugs successfully protected mice from smoking-induced lung cancer.

Until now, it has been difficult to study chemoprevention because no good animal model of smoke-related cancers existed. Previous studies investigating chemoprevention have used components of cigarette smoke, but not the complete, complex mixture of cigarette smoke, either mainstream or environmental. The authors developed a model in which mice could be exposed to mainstream cigarette smoke and fed chemopreventive agents. First, they established that the smoke caused lung tumors; then, they showed that three chemopreventive agents – budesonide, phenethyl isothiocyanate (PEITC), and N-acetyl-L-cysteine (NAC) – could protect the mice, reducing the number of tumors that formed.

All three agents protected current smokers from developing lung tumors; when given to ex-smokers, mice who were no longer being exposed to cigarette smoke, the budenoside retained its protective ability, while the PEITC became less effective. These results make sense in light of what is known about the drugs' mechanisms of action: Budenoside acts as an anti-inflammatory agent, able to act against cancer at various stages. PEITC acts by altering the metabolism of carcinogens. The strength of this study lies in the animal model, which appears to be useful for evaluating both the effectiveness and the toxicity of the chemopreventive agents: both the budenoside and the PEITC seemed to be harming the liver after 7 months of treatment. Still, the finding that chemopreventive agents can protect against smoke-induced lung cancer could lead to promising new strategies for cancer prevention.

Stem Cells Target Tumors

Mercapide et al., pp. 1206–1215

Glioblastoma multiforme is one of the most common and deadliest brain tumors; patients rarely survive 2 years after diagnosis. Recently, researchers have explored new therapies in which neural stem/progenitor cells (NSPC) deliver tumor-killing drugs directly to the cancerous cells. Mercapide et al. investigated whether NSPC, engineered to churn out an antitumor agent, could hunt down and destroy the tumor cells. It appears that they can, at least in mice.

The usefulness of neural stem cells originates in the tumors themselves: the very factors that stimulate the cancer cells' persistent proliferation (VEGF, for one) also excite the NSPC, spurring them to make their way toward the tumor. As they begin differentiating, they release chemicals that stop the cancer cells from reproducing. In this study, the authors tested NSPC genetically engineered to produce an enzyme that activates cyclophosphamide (CPA), a chemotherapy drug that halts proliferation.

First, they established that, in cell culture, NSPC sought out the glioma cells and fused with them. Next, they injected the engineered NSPC into the brains of mice with glioblastomas. When they gave the mice CPA, the enhanced NSPC sprung their trap, activating the CPA, impeding tumor growth, and reducing the tumor volume. Even when the NSPC were injected far from the tumors, they selectively targeted the glioma and moved in for the kill. These findings indicate great potential for neural stem cells in the treatment of brain tumors. 1

Illustration 1. Neural stem cells (arrowhead/green) make their way to a brain tumor (T), targeting the cancer cells for destruction