In Clinical Cancer Research this week, researchers in Japan and the US report on the role of epigenetic silencing of microRNA-34b/c in the pathogenesis of malignant pleural mesothelioma. The team examined aberrant methylation and expression of miR-34s in malignant pleural mesothelioma cell lines and tumors. They found aberrant methylation in two of six cell lines and 13 of 47 tumors in miR-34a, and found aberrant methylation in all six cell lines and 40 out of 47 tumors in miR-34b/c. "Expression of miR-34a and 34b/c in all methylated cell lines was reduced and restored with 5-aza-2'-deoxycytidine treatment," the authors write. "The forced over-expression of miR-34b/c, but not p53, showed a significant antitumor effect with the induction of apoptosis in malignant pleural mesothelioma cells."
Also in Clinical Cancer Research this week, researchers from the National Cancer Institute investigate HER2-Affitoxin as a potent therapeutic agent for the treatment of HER2 over-expressing breast cancer. The team developed and characterized a novel recombinant protein, "combining an HER2-specific Affibody and modified Pseudomonas aeruginosa exotoxin A, which, after binding to HER2, is internalized and delivered to the cytosol of the tumor cell, where it blocks protein synthesis by ADP ribosylation of eEF-2." In vitro experiments showed that HER2-Affitoxin eliminated HER2 over-expressing cells at low concentrations, and efficacy studies show the complete eradication of relatively large BT-474 tumors, and significant effects on SK-OV-3 and NCI-N87 tumors. "Our findings showed that HER2-Affitoxin is an effective anticancer agent and a potential candidate for clinical studies," the authors write.
Finally in Clinical Cancer Research this week, researchers in South Korea investigate the use of FDG-PET imaging as a tool for selecting which advanced non-small-cell lung cancer patients may be spared maintenance therapy. The team studied 43 patients who underwent baseline FDG-PET scan and didn't show disease progression after four cycles of primary chemotherapy. Percent increase in maximum standard uptake value in the late disease progression subgroup was greater than those in the early disease progression subgroup, the authors write. "Fractional decrease in maximum standard uptake value of the main lesion after completion of four cycles of chemotherapy may discriminate patients with [time-to-progression of eight weeks or greater,] and predict time-to-progression and overall survival in patients with advanced non-small-cell lung cancer," they add.