In Cancer Research this week, researchers in France say that formation of the eIF4F translation-initiation complex determines a patient's sensitivity to anti-cancer drugs, particularly those that target EGFR and HER2 receptors. Trastuzumab, cetuximab, and erlotinib all decrease the formation of the eIF4F complex in breast, colon, and head and neck cancer cells, respectively, the researchers write. Ectopic expression of eIF4F restores the trastuzumab-dependent defect in eIF4F formation, makes cells resistant to the decrease in cell proliferation mediated by trastuzumab, and makes breast cancer xenografts resistant to trastuzumab inhibition. "In breast tumor specimens, the level of eIF4E expression is associated with the therapeutic response to a trastuzumab-based regimen. Together, our findings suggest that formation of the eIF4F complex may be a critical determinant of the response to anticancer drugs that target HER2 and epidermal growth factor receptor," the authors add.
Also in Cancer Research this week, researchers in Denmark and Italy say that MMSET — a SET domain–containing histone lysine methyltransferase — is highly expressed in neuroblastoma and is associated with aggressiveness in patients with the disease. The researchers found that the MMSET protein is positive in 75 percent of neuroblastomas they studied, and that its expression level was significantly associated with poor survival, negative prognosis, and metastatic disease. MMSET is also required for proliferation of neuroblastoma cells and brain-derived neural cells, suggesting that it supports proliferation of progenitor cells in neuroblastomagenesis by regulating their differentiation. "MMSET might be a strong candidate therapeutic target in a subset of neuroblastomas with unfavorable prognosis," they add.
And finally in Cancer Research this week, researchers in the US and Europe present findings from a study of a novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis. The team generated mice with inactivation of JAM-C, and found that they displayed significantly decreased B16 melanoma cell metastasis to the lung. Treatment of mice with soluble JAM-C prevented melanoma lung metastasis, the authors add, suggesting JAM-C could represent a novel therapeutic target for melanoma metastasis.