US Pharm. 2007;32(10)(Oncology suppl):27-28.

Key Myeloma Mechanism Discovered
In a discovery that might lead to a greater understanding of how multiple myeloma starts and how to best treat the disease, researchers from the National Cancer Institute (NCI)  have identified changes to molecules in cancer cells that activate the NF-kappaB signaling pathway, which has an important role in cancer cell growth and survival. The researchers found that the NF-kappaB pathway was activated in most of the multiple myeloma cells they looked at. When they used an inhibitor of a primary enzyme, called lkappaB kinase beta, required to activate this pathway, the cancer cells either died or stopped dividing. Multiple myeloma is expected to result in nearly 11,000 deaths and almost 20,000 new cases this year in the U.S. The results of the research were published in the August issue of Cancer Cell.

"This signaling pathway prevents cell death and therefore this study suggests inhibitors of the NF-kappaB pathway would provide a rational approach to the treatment of this cancer," said NCI Director John E. Niederhuber, MD.

More Schooling Linked to Lower Cancer Risk
More years of education translates to a lower risk of death from cancer, according to a database study by researchers from the American Cancer Society. The study found that men with 12 or fewer years of education died from cancer at more than twice the rate of those with more schooling. The results of the study, which looked at death certificates and census data for 2001 in 47 states and the District of Columbia, also found a similar but lower link between education and cancer mortality for women. 

Some other interesting findings emerged from the study. For example, researchers found that African American men with 12 or fewer years of education had a prostate cancer death rate of 10.5 per 100,000, compared with 4.8 per 100,000 for those with more education. In another novel finding, which contradicts earlier study results, women with less education experienced higher breast cancer death rates than women with more education.

Tumor Protein May Enable Early Lung Cancer Diagnosis
The existence of a protein in nearly all lung cancers is raising the possibility of a serum biomarker that could permit early diagnosis of more patients. Detectable levels of human aspartyl (asparaginyl) beta-hydroxylase (HAAH) were found in nearly all lung cancer patients tested, researchers reported at a conference sponsored by the American Association for Cancer Research.

"Elevated serum HAAH in conjunction with CT scanning may greatly facilitate early diagnosis of lung cancer at a stage in which cure rates are significantly higher and thus may contribute to increased patient survival," said Mark Semenuk, of Panacea Pharmaceuticals, the company that developed the assay for HAAH. Semenuk and colleagues measured serum levels in 160 patients with lung cancer, a control group of 93 people with no evidence of cancer, and 50 smokers with no evidence of cancer. None of the control group evidenced HAAH; however, the protein was found in 99% of the lung cancer patients. Among smokers participating in the study, the average HAAH level was 0 ng/mL. Four people from this group had serum levels above the diagnostic threshold of 3 ng/mL, although they were not known to have cancer.

Work is underway to determine the value of HAAH as a prostate cancer detection test, possibly as a follow-up tool for evaluating men with elevated prostate-specific antigen levels.

Inflammation Connected to Lung Cancer
It is well known that smoking leads to lung cancer, but new research results might explain how. According to researchers at the National Cancer Institute and M.D. Anderson Cancer Center, the genes involved in the inflammation response may lead to increased lung cancer risk. These findings, published in the July 1 Cancer Research, might help explain how smoking tobacco actually leads to the disease. In a case-control study of 3,283 volunteers--including 1,553 patients with lung cancer--researchers studied a panel of 59 single nucleotide polymorphisms in 37 genes involved in the inflammatory pathway. Five of these genes showed a strong association to lung cancer, although the researchers said the only a mutation of the gene for interleukin 1-beta, named C3954T, was a likely true risk factor. The C3954T gene produced a 27% increased risk of lung cancer.

"Our findings help explain how heavy smoking, for example, combines with a genetic predisposition to create a besieged environment within the lungs," said Eric Engels, MD, of the National Cancer Institute. "Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA."

HIV Drugs Might Also Combat Certain Cancers
Some protease inhibitors that are used with other drugs to treat HIV infection may also help fight certain types of cancer, according to a report in the September 1 Clinical Cancer Research. Nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Invirase) interfered with the growth of several types of cancer cells in laboratory tests. When administered in doses known to be safe in HIV patients, the drugs inhibited growth of non­ –small cell lung cancer as well as every cell type in a panel of 60 human cancer cells. The researchers focused on these drugs because they are known to inhibit the activation of Akt, a protein linked to the development of many cancers, such as non–small cell lung cancer. 

"Repositioning drugs that are already FDA-approved for use in humans could greatly accelerate the development of new cancer therapies," according to Phillip A. Dennis, MD, PhD, of the Medical Oncology Branch of the NCI Center for Cancer Research. Dr. Dennis' team recently began a new clinical trial to test nelfinavir in cancer patients.


Another Grape Skin Extract Shows Promise
Muscadine grape skin extract (MSKE) can interfere with the growth of prostate cancer cells, laboratory tests show. Investigators from the National Cancer Institute said their research indicates that the muscadine grape does not contain significant amounts of resveratrol, another grape skin component common in the red grapes used to make red wines, which has been widely shown to inhibit prostate cancer growth. The results of the research, published in the September 1 Cancer Research, might offer researchers another weapon in the fight against prostate cancer.

"These results show that MSKE may have potent antitumor activities in the lab that differ from the effects of resveratrol," said Jeffrey E. Green, MD, chief of the Transgenic Oncogenesis and Genomics Section of the NCI's Center for Cancer Research. Dr. Green said that more studies are needed to tell if MSKE can prevent or treat the disease.

Deaths from Breakthrough Pain Drug Produce Warnings from Manufacturer
Adverse events, including death, have been linked to fentanyl buccal tablets (Fentora), a drug for breakthrough pain in cancer patients who are opioid-tolerant, according to the FDA. The drug's maker, Cephalon, issued letters warning physicians of the risks and outlining a rigid set of recommendations for the drug's use. The deaths occurred "as a result of improper patient selection (e.g., use in opioid non-tolerant patients), improper dosing, and/or improper product selection," said the FDA.

The drug is indicated only for management of breakthrough pain in cancer patients with persistent pain who are already receiving and are tolerant to opioid therapy. In the letters, Jeffrey M. Dayno, MD, vice-president of medical services at Cephalon, issued these warnings: "Do not use Fentora in opioid non-tolerant patients; use Fentora only for labeled indications; do not prescribe the drug for patients with acute pain, postoperative pain, headache/migraine, or sports injuries;  be aware that Fentora is not a generic version of Actiq, therefore do not substitute Fentora for Actiq or other fentanyl-containing products."

Colorectal Cancer Patients Living Longer with Newer Chemo Regimens, but at a Price
New chemotherapy regimens are prolonging survival rates among patients with colorectal cancer, but at a cost of high toxicity and other complications. Patients who were expected to live for a year when treated with fluorouracil and leucovorin, for example, survived for an additional eight months with the addition of irinotecan plus bevacizumab, researchers from the University of Ioannina, Greece, reported in the September 20 Lancet Oncology. They also noted an additional survival benefit of 4.7 months with the addition of oxaliplatin plus bevacizumab or for irinotecan plus oxaliplatin. The newer chemotherapy drugs can cause various complications, however, such as thrombotic events, severe hematological toxicity, diarrhea, neurosensory disorders, and gastrointestinal perforation.

The researchers pointed out that because the study was a meta-analysis based on group data and not individual patients, conclusions about the value of specific regimens are premature. "Our meta-analysis concludes that progress has definitely been made in this area of research, but the existing uncertainties suggest that more data are needed, especially for the newest regimens,"said John P.A. Ioannidis, MD, PhD, of the University of Ioannina.

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