Highlights of This Issue

Abstract

NSCLC with mutations in the EGF receptor often develop resistance to first-line targeted therapy. The mucin 1 C-terminal (MUC1-C) oncoprotein associates with EGFR and is aberrantly overexpressed in NSCLC. Here in NSCLC cells harboring EGFR mutations, unanticipated findings demonstrate that targeting MUC1-C with stable silencing, expression of a DN mutant, or treatment the MUC1 inhibitor (GO-203) results in downregulation of EGFR signaling and inhibition of growth, clonogenic survival, and tumorigenicity. Of therapeutic relevance, GO-203 and the irreversible EGFR inhibitor afatinib were found to be more effective in combination in inhibiting survival of EGFR mutant NSCLC cells than either agent alone. These findings highlight the novelty of MUC1-C in driving activation of mutant EGFR signaling in NSCLC cells.Cisplatin and platinum derivatives are first-line chemotherapeutic agents in ovarian cancer treatment, but are associated with high toxicity and frequent relapse with a platinum-resistant disease. In the present study, Casagrande and colleagues demonstrated that the liposomal formulation of cisplatin, lipoplatin, was active in cisplatin-resistant ovarian cancer cells, inhibited cell migration, decreased cancer stem cells, synergized with doxorubicin and Abraxane and reduced by more than 90% tumor xenograft growth with low toxicity. The major clinical implication of the study is to provide a rationale for lipoplatin clinical assessment in cisplatin-resistant recurrent ovarian cancer patients.To discover genetic mechanisms underlying ameloblastoma pathogenesis, Brown and colleagues evaluated a cohort of ameloblastomas and other odontogenic tumors using a combination of molecular techniques. Activating, mutually exclusive FGFR2-RAS-BRAF mutations were found in 88% of ameloblastomas. Among odontogenic tumors, BRAF mutations were specific for those with ameloblastic epithelium. BRAF mutations were also associated with younger age, and the absence of BRAF was associated with early recurrence and maxillary location. In vitro studies suggest a role for targeted therapy. This work lends significant understanding to the genetic underpinnings of ameloblastoma, highlighted by findings with diagnostic, prognostic, and therapeutic implications.Radiation-related lymphopenia is frequently observed with fractionated external beam radiotherapy and is associated with reduced survival. Targeting the mechanisms underlying this poorly understood phenomenon could improve treatment response. Kuo and colleagues investigated the role of Galectin-1, an immunomodulatory B-galactoside-binding protein, and found that radiation enhances Gal-1 secretion in NSCLC and that its tumor secretion significantly influences the level of circulating T lymphocytes after tumor irradiation while augmenting tumor growth and metastasis. As an exciting new target to combine with radiotherapy, Gal-1 blockade could improve curability in NSCLC through the prevention of radiation-related lymphopenia and immune suppression within the tumor microenvironment.