Highlights of This Issue

Abstract

A gender bias exists in the development of gliomas. Females are at lower risk than males, implicating estrogen-mediated protective effects. Sareddy and colleagues observed decreased ERβ expression during glioma progression and examined potential use of ERβ agonists as a novel therapeutic to curb the growth of gliomas. Agonists promoted both expression and tumor suppressive functions of ERβ in gliomas. Liquiritigenin, a plant-derived ERβ agonist, significantly reduced in vivo growth of gliomas. ERβ agonists could represent a novel class of drugs to treat gliomas and provide an additional tool for enhancing survival.EGFR signaling is a key pathway in the growth control of many cancers, whose activity can be modulated by small molecule EGFR kinase inhibitors. This article describes the identification of proteins, through multiscale quantitative proteomics, whose presence or change in abundance is a biomarker of cancer cell response to the inhibition of EGFR tyrosine kinase. Kani and colleagues posit and then verify that proteomic discovery in in vitro tissue culture models can identify proteins with concordant in vivo behavior and further, can be a valuable approach for identifying tumor-derived serum proteins. This area of inquiry has significant biologic and clinical implication across many cancers, but most notably in lung cancer.To improve the activity of bortezomib against DLBCL cells, a novel strategy was developed combining the irreversible proteasome inhibitor carfilzomib with the pan-BH3 mimetic obatoclax. This regimen exhibited highly synergistic in vitro activity against both GC- and ABC-DLBCL cells as well as their bortezomibresistant counterparts. Notably, combined treatment resulted in significant activity and increased survival of tumor-bearing mice in vivo. Mechanisms underlying synergism were multifactorial, including JNK activation, Noxa upregulation, and untethering of Bak from Mcl-1/Bcl-xL. This dual-targeted approach has potentially important clinical implications for the treatment of DLBCL patients who might not otherwise respond to standard proteasome inhibitor therapy.Levallet and colleagues found an adverse prognostic effect of class III β-tubulin (TUBB3) tumor immunostaining in 412 NSCLC patients and TUBB3 expression associated with resistance to chemotherapy. TUBB3 content correlated with K-Ras mutations in a subset of 208 cryopreserved specimens. Human bronchial epithelial cells expressing a mutant form of K-Ras had a significantly higher content of TUBB3 protein as compared to their isogenic counterpart expressing wild-type K-Ras. Short interfering RNA K-Ras knockdown or inhibition of RAF/MEK/PI3K signaling pathways by pharmacological inhibitors downregulated TUBB3 expression in bronchial cells. These findings deserve further studies evaluating anti-MEK or anti-PI3K drugs in NSCLC patients with TUBB3-overexpressing tumors.