NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
August 10, 2004 • Volume 1 / Number 32 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Studies Suggest Potential Link between HCV and NHL

Two case-control studies, one conducted in the United States and the other in Spain, have confirmed earlier findings of a possible link between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL). The studies' authors stressed, however, that it remains unclear whether HCV infection is associated preferentially with specific lymphoma subtypes. Both studies were published in the August International Journal of Cancer.

The population of the U.S.-based study came from four areas covered by the NCI Surveillance, Epidemiology, and End Results (SEER) program. Overall, 32 of the 813 patients (3.9 percent) with NHL were HCV infected, compared with 14 of 684 controls (2.1 percent). Even after adjusting for potentially confounding factors such as drug use and blood transfusion history, there was a nearly two-fold increase in NHL risk associated with HCV. In the Spanish study, which involved more than 1,100 participants, after excluding patients with HIV and those who had undergone organ transplantation, HCV was associated with a 58 percent increased risk of NHL.

The studies' findings are consistent with a number of earlier studies conducted in the United States and Europe, particularly Italy, in which HCV prevalence among NHL patients was as high as 37 percent. Other biological evidence tends to support such a link, explained Dr. Eric A. Engels of NCI's Division of Cancer Epidemiology and Genetics, the lead author of the U.S. study. For example, he noted that HCV infection has been linked to essential mixed cryoglobulinemia, a disorder that can evolve into NHL. In addition, patients with HCV infection often have chromosomal mutations that are associated with a high risk for NHL. In a study published in 2002, patients with splenic marginal zone NHL who were treated for HCV with an interferon-α-based regimen also saw complete regression of their NHL.

Even if HCV is confirmed to be a causal agent of NHL, Dr. Engels adds, "Most NHL cases in the United States would not be due to HCV because HCV infection is fairly uncommon in the United States and the HCV-associated relative risk is somewhat low."

Gene Transfer Technique Stimulates Immune System to Kill Tumor Cells

When normal cells are harmed by cancer treatments, the patient suffers. However, scientists at Minnesota's Mayo Clinic report that, in mice with metastatic melanoma, killing some of a class of normal skin cells stimulates the mice's immune systems to attack tumors throughout the body. They are the first to successfully demonstrate these effects using gene transfer.

Their "simple method to cure established tumors" by killing normal cells was published online in Nature Biotechnology on August 1. The researchers, led by Dr. Gregory Daniels, targeted normal melanocytes, pigment-producing cells in the skin and eyes which become cancerous in melanoma. To target the mice's melanocytes, researchers injected several compounds into the skin. Injections contained a circular piece of DNA with gene coding for HSVtk, a viral protein which converts the drug ganciclovir - also administered in the study - into a toxic form. The HSVtk plus ganciclovir combination killed normal melanocytes, stimulating the immune system, especially when cytomegalovirus was also injected into the skin.

Where melanocytes died, large, dense stretches of immune cells congregated. Melanocyte death appeared to break down some of the immune system's self-tolerance, which ordinarily protects melanoma tumor cells. All mice given HSVtk, ganciclovir, and cytomegalovirus treatment three times were cured of established melanoma. After 100 days, none showed evidence of cancer.

The researchers, whose work was funded in part by the National Institutes of Health (NIH), write that their approach "represents an important opportunity for the development of biological therapies for cancer." They note that in the clinical setting, doctors would have to design treatment carefully, taking into account such variables as tumor size and number of vaccinations, in order to decrease patients' risk of autoimmune disease.

Specific Signaling Pathway Activation Appears to Influence Gefitinib Response

Patients with non-small-cell lung cancer (NSCLC) whose tumor cells overexpress a specific signaling pathway appear to respond better to the targeted agent gefitinib (Iressa) than those in whom the pathway is not activated, according to a study published in the August 4 Journal of the National Cancer Institute (JNCI). Time to progression, response rate, and disease control rate were significantly better in patients with tumor cells in which the Akt signaling pathway was active, researchers from the Bellaria Hospital in Italy reported.

To conduct the study, the researchers measured the activity of the Akt and MAPK pathways - which are commonly overexpressed in lung, pancreatic, thyroid, and ovarian cancers - in 103 patients before gefitinib treatment. Patients whose tumors were positive for Akt phosphorylation, a measure of pathway activity, fared better than those whose tumors were negative for Akt phosphorylation. MAPK pathway status appeared to have no influence on response to the drug. Patients with an activated Akt pathway tended to be female and never have smoked.

Gefitinib, a drug that targets the epidermal growth factor receptor (EGFR), has proven to be remarkably effective in a small percentage of patients with NSCLC for whom other treatments have failed. As a result, researchers have been working to determine what genetic or molecular factors may influence gefitinib response. In April, two separate research teams reported that they had found specific EGFR mutations that correlated with patients' clinical response to gefitinib (see May 4 NCI Cancer Bulletin). In a related editorial in JNCI, Dr. Mark G. Kris and colleagues from Memorial Sloan-Kettering Cancer Center, argued that the findings from the Italian study "do not supersede better predictors of response to gefitinib," referring to the studies published in April. "When patients with NSCLC enter the clinic today, treatment decisions must be guided by both clinical characteristics and EGFR mutation status," they said.