Version of Record online: 24 APR 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 1, page ix, 1 July 2007
How to Cite
Seydel, C. (2007), Spotlight. Int. J. Cancer, 121: ix. doi: 10.1002/ijc.22825
- Issue online: 24 APR 2007
- Version of Record online: 24 APR 2007
Erionite and Asbestos
Bertino et al., pp. 12–20
Like asbestos, the mineral erionite can transform human mesothelial cells, leading to malignant mesothelioma (MM). Unlike asbestos, erionite can do its damage without the aid of SV40, according to this study by Bertino et al. The findings could explain the high rate of MM in the Cappadocia region of Turkey, where SV40 has not been isolated. They also suggest that the hazard of exposure to similar fibers should be carefully evaluated.
Erionite, a ubiquitous zeolite, is a strong mutagen and induces a high incidence of MM in rats who inhale it. Exposure to erionite fibers leads to the creation of reactive oxygen metabolites from macrophages and turns up transcription of early response proto-oncogenes. Earlier work has shown that asbestos fibers-induced transformation of cells was enhanced by SV40 infection acting through the PI3K/Akt signaling pathway. In the current study, the authors looked at how efficiently erionite transformed human mesothelial cells in the absence of SV40, compared with two varieties of asbestos – amosite and chrysotile. They also investigated signal transduction in the transformed cells to better understand the mechanism by which the mineral fibers spur transformation.
Cells exposed to erionite began proliferating faster within 24 hours. The erionite fibers were less toxic to cells than the amosite, allowing a high proliferation rate. Chrysotile asbestos, although not as toxic to cells as amosite, could not promote proliferation. The cells showed the morphologic changes associated with full transformation. Obviously, erionite transforms cells in the absence of SV40.
Familial Aggregation of Cancer
Gorlova et al., pp. 111–118
Relatives of people who have had lung cancer but have never smoked appear to have a higher risk for cancer, particularly young-onset cancers, according to a new case-control study from Gorlova et al. The study, which included nearly 5,000 people, contradicts some earlier reports and could indicate that shared genetic factors could predispose individuals to lung cancer and several other cancers.
Several previous studies have reported no increased risk of lung cancer in immediate relatives of lung cancer patients who have not smoked. One study, based on a small number of participants, reported a 6-fold increase in lung cancer patients. Because individuals who have never smoked and who develop lung cancer may represent a distinct, genetically susceptible population, identifying familial aggregation of cancers could help illuminate genetic factors that contribute to lung cancer susceptibility.
Gorlova et al. analyzed data from 2,465 relatives of 316 nonsmoking lung cancer patients and 2,441 relatives or 318 never-smoking controls to compare the groups' risk of lung cancer and other cancers. The authors identified a 25% increase in risk of any type of cancer among first-degree relatives of lung cancer patients and a 44% increase in risk of cancer occurring before age 50, compared with relatives of controls. Certainly, shared environmental factors, such as secondhand smoke from parental smoking, could cause multiple family members to develop cancer with no shared genetic vulnerability. In this study, there was a slightly higher number of smokers among relatives of controls than lung cancer cases, and parental smoking does not seem to influence the conclusions. The authors controlled for smoking status and conducted analyses stratified by smoking status, and therefore conclude that genetic factors remain the more likely explanation for the familial aggregation of cancers that they observed.
Rapamycin and Herceptin Team Up
Wang et al., pp. 157–164
The one-two punch of rapamycin and herceptin administered together fights breast cancer better than rapamycin alone, says a new study from Wang et al. The results, which confirm earlier work showing increased susceptibility of certain breast cancer cells to inhibitors of the PI3 kinase signaling pathway – such as rapamycin – could improve breast cancer treatment strategies.
About a third of breast cancers overexpress ErbB2, a member of the epidermal growth factor receptor (EGFR) family. Overexpression of ErbB2 is associated with a high relapse rate and poor clinical prognosis, and ErbB2 plays a functional role in cell transformation and mammary cell carcinogenesis. Breast cancer cells that overexpress ErbB2 are particularly sensitive to rapamycin, which interferes with cell cycle progression and halts tumor growth. Rapamycin and its analogs are being developed as anticancer drugs alone and in combination with other agents.
In this study, the authors investigated rapamycin's effectiveness when paired with herceptin, a monoclonal antibody against ErbB2. In clinical trials, herceptin achieves a 15-30% response rate in breast cancers overexpressing ErbB2. The new results demonstrate that rapamycin and herceptin together inhibit the growth of ErbB2-overexpressing cancer cells in culture and in mouse xenograft and transgenic models more effectively than each component by itself.