More vitamin D could help prevent lung cancer recurrence
Researchers at the University of Michigan Comprehensive Cancer Center report in the February 15, 2011 issue of the journal Clinical Cancer Research that an enzyme elevated in lung cancer that reduces the active form of vitamin D is associated with more aggressive tumors and worse survival. The finding could aid the development of an agent to protect against the return of the disease following surgery.
Recent research suggests a preventive role for vitamin D against lung cancer as well as a benefit for the vitamin in lung cancer survival. For the current study, University of Michigan School of Medicine associate professor of internal medicine Nithya Ramnath, MD and colleagues evaluated tumor samples from 86 patients with lung adenocarcinoma to determine the level of CYP24A1, which encodes an enzyme that is overexpressed in many cancers. This enzyme breaks down calcitriol (1-alpha,25-dihydroxyvitamin D3), which has an antiproliferative effect in lung adenocarcinoma and other malignancies. The team found that CYP24A1 expression was 8 to 50 times higher in cancerous compared to healthy lung tissue. Patients with higher levels of CYP24A1, who comprised approximately one-third of the subjects, had an increased likeliness of aggressive tumors and a 42 percent chance of survival after five years compared with an 81 percent chance for those with low CYP24A1. In experiments with lung cancer cell lines, cells that expressed high levels of CYP24A1 were demonstrated to be more resistant to treatment with calcitriol compared to those with low CYP24A1.
"Half of lung cancers will recur after surgery, so it's important to find a way to prevent or delay this recurrence," Dr Ramnath remarked. "A natural compound like vitamin D is attractive because it has few side effects, but it's even better if we can determine exactly who would benefit from receiving vitamin D."
Scientists are now attempting to identify compounds that block CYP24A1, which would increase vitamin D's anticancer potential, and could be combined with vitamin D treatment.
The concept of customized chemotherapy involves predicting how well proposed chemotherapy drugs will kill a patient’s cancer or lower the patient’s risk of adverse effects (Von Hoff DD 1990) before they are given to the patient. It is critical to extending survival time (Thunnissen FB et al 2006). Molecular markers in patients’ tumors can help predict response to specific chemotherapy drugs.
Iressa® treatment is linked with favorable survival in NSCLC patients whose tumors have low levels of ribonucleotide reductase (Huang CL et al 2006; Kwon WS et al 2006).
The ability of 5-fluorouracil to kill lung cancer cells depends on the activity of dihydropyrimidine dehydrogenase and thymidylate synthase in patients’ tumors (Ploylearmsaeng SA et al 2006; Takizawa M et al 2006).
The responsiveness of NSCLC to Iressa® and Tarceva® depends on the presence of epidermal growth factor receptor (EGFR) mutations in the tumor (Tokumo M et al 2006).
The response to Taxol® and Navelbine® depends on tubulin III and stathmin mRNA levels in tumor cells. High levels of tubulin III are associated with a poor response to chemotherapy and a shorter progression-free survival (Seve P et al 2005).
If the tumor shows BRCA1 and ERCC1 (genes involved in DNA repair pathways), then cisplatin, carboplatin, and taxanes will not be effective in killing the tumor, resulting in poor survival (Rosell R et al 2006; Santarpia M et al 2006).
Vitamin D improves survival in early-stage non-small cell lung cancer (NSCLC) patients (Zhou W et al 2005). Therefore, vitamin D supplementation is recommended for lung cancer patients planning to undergo surgery, particularly during the winter season, and especially for those with darker skin, and for vegans who have limited sun exposure. Experimental studies show that vitamin D protects against lung cancer progression by preventing cancer spread (metastases) (Wiers KM et al 2000). Sources of vitamin D include sunlight, milk, and darkly colored fish.
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