Spotlight

Treating One Cancer Can Bring On Another

Rapiti et al., pp. 1141–1145

Radiation can act as a double-edged sword, creating a new cancer even as it is used to kill an existing malignancy. Rapiti et al. investigated whether radiotherapy used to treat prostate cancer could increase the risk of colon and rectal cancers. They found a significant increase in colon, but not rectal cancers in the years following radiation treatment for prostate cancer.

The Geneva Cancer Registry keeps record of all incident cancer cases occurring in the area, including data regarding treatment, survival status and cause of death. The authors used data from this registry to evaluate the risk of colorectal cancer among prostate cancer patients who had survived at least 5 years after diagnosis. This allowed time for development of radiation-induced cancers. Previous analyses have disagreed about whether long-term prostate cancer survivors who have received radiation therapy develop more rectal and colon cancers than those who were treated by surgery only.

Although increased diagnostic surveillance of prostate cancer survivors could account for an increase in colon and rectal cancer risk, the authors found no such increase in nonirradiated patients, suggesting that the observed increase stemmed from the radiation itself. Also, increased risk to irradiated patients occurred 5 to 9 years after prostate cancer diagnosis, a reasonable time frame for radiation-induced cancers to develop. These findings illuminate a serious long-term side effect of radiotherapy, but current treatment techniques expose less adjacent tissue to high-intensity radiation, probably reducing the risk of stimulating additional cancers.

Cell Surface Receptor Might Hold the Key to Leukemia

Danesh Manesh et al., pp. 1190–1195

An ideal target for cancer therapy is a molecule that is amply expressed by the malignant cells, yet absent from healthy cells, and Ror1 appears to be just that. The receptor tyrosine kinase studs the surface of leukemia cells but never appears on normal white blood cells, according to this report from Danesh Manesh et al.1.

The ROR1 gene is not expressed in healthy donor cells (first lane) but clearly present in leukemia cells (lanes 2–5).

Previous studies had shown that chronic lymphocytic leukemia (CLL) cells express 44 times as much Ror1 as normal cells do. Ror receptors participate in signal transduction, cell-cell interaction and regulation of proliferation and are highly conserved among species, indicative of their importance to the cell. The team used RT-PCR to demonstrate that leukocytes of CLL patients contained Ror1 RNA, while healthy donor cells did not. They then showed that CLL cells produce Ror1 protein, while normal B cells produce none. High expression of Ror1 was seen in CLL patients with mutated immunoglobulin heavy chain variable (IgVH) genes, who have a better prognosis, as well as in those with unmutated IgVH, whose prognosis is worse.

Because it is overexpressed in CLL cells, Ror1 should be pursued as a candidate for therapeutic interventions. In addition, it is not limited to CLL, but also induced in other tumors as well, potentially expanding its usefulness.

Looking at Lignans: How They Slow Breast Cancer

Saarinen et al., pp. 1196–1204

Epidemiological studies have suggested that the plant lignan lariciresinol cuts the risk of breast cancer. No one knows exactly how the compound thwarts the disease, however. Saarinen et al. investigated the effect of feeding lariciresinol to rats and mice with mammary tumors. The compound, they showed, inhibited the growth of the tumors, a result that could have considerable importance for human cancer prevention.

Fiber-rich foods such as whole grains, vegetables and fruits contribute naturally occurring phenolic compounds to one's diet. Some of these compounds, classified as phytoestrogens, might influence the progression of estrogen-related diseases, like breast cancer. Researchers have found a link between consumption of phytoestrogens, in the form of dietary lignans, and reduction in breast cancer risk. Lariciresinol is one of the most abundant plant lignans in a Western diet, and when it is ingested, the body metabolizes it into enterolignans, which have been shown to stop breast cancer growth in experimental models. A recent epidemiological study showed that high lariciresinol intake associates with low breast cancer risk, but no one has established a cause-effect relationship between eating lariciresinol and preventing cancer. To explore that question, Saarinen et al. induced tumors in rats, then fed them lariciresinol, and found that the compound impeded the tumors' growth – particularly the tumors that developed while the rats were receiving the treatment, rather than those tumors that developed before the treatment started. They also gave lariciresinol to mice bearing human mammary tumors maintained by estradiol.

After 9 weeks, tumor weights were much lower in the mice consuming the phytoestrogen than in those who did not partake. The researchers also demonstrated for the first time that both the rats and mice metabolized the lariciresinol into enterolignans, as humans do. One of these, enterolactone, was shown to impede VEGF secretion, suggesting that the compound does its work by slowing the tumor's blood vessel development. Additionally, the lariciresinol-containing diet induced apoptosis in the tumor cells. These findings provide concrete support for the role of diet in breast cancer prevention.