In the British Journal of Cancer this week, researchers in Japan explore the effects of a κ-opioid receptor agonist on non-small-cell lung cancer cells. The researchers applied the agonist to both gefitinib-resistant and gefitinib-sensitive lung cancer cells and found that it produced a concentration-dependent decrease in the cells' growth. Further, the agonist enhanced the growth-inhibiting effect of gefitinib in the treatment-sensitive cells and caused a concentration-dependent decrease in phosphorylated-glycogen synthase kinase 3β in the treatment-resistant cells, which also reduced growth, the team adds.
Also in the British Journal of Cancer, researchers in the UK characterize multi-drug resistance protein 1 — which can lead to treatment resistance in cancer cells — in human mitochondria. The team examined expression levels of MRP-1 in both normal and cancer tissues and detected the protein in the mitochondria of both. "Treatment with a non-lethal concentration of doxorubicin increased mitochondrial and plasma membrane MRP-1, increasing resistance to MRP-1 substrates," the authors write. "Mitochondrial MRP-1 may be an exciting new therapeutic target where historically MRP-1 inhibitor strategies have limited clinical success."
Finally in the British Journal of Cancer, researchers in New Zealand analyze the effect of stromal-targeting agent DMXAA on melanoma xenografts. The team analyzed melanoma cell-specific and stromal cell-specific gene expression in the xenografts before and after treatment with DMXAA, and found that it activated pro-inflammatory signaling pathways in both stromal and cancer cells. This led to "neutrophil accumulation and haemorrhagic necrosis and a delay in tumor re-growth of 26 days in A375 melanoma xenografts," the authors write. "[DMXAA] and related analogues may potentially have utility in the treatment of melanoma. The experimental platform used allowed distinction between cancer cells and stromal cells and can be applied to investigate other tumor models and anti-cancer agents."