Highlights of This Issue

DOI: Published June 2014

Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma

Nakaoku et al. Page 3087

Multiple oncogene fusions, involving the NRG1, ERBB4, BRAF, ALK and RET genes, were identified as drivers for development of invasive mucinous adenocarcinoma (IMA) of the lungs. These fusions, and BRAF and EGFR activating mutations, occurred in approximately 15% of IMA cases. The aberrations were exclusively detected in cases without KRAS mutation, a known major oncogene aberration in IMA. These fusions represent therapeutic targets for tyrosine kinase inhibitors (TKIs) approved for clinical use, in addition to BRAF and EGFR mutations.

Inhibition of RTKs and mTOR in MPNST

Patwardhan et al. Page 3146

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive and therapeutically resistant tumors with gene amplification for receptor tyrosine kinases (RTKs) such as c-Kit and PDGFR. Patwardhan and colleagues tested the efficacy of imatinib and PLX3397, a selective c-Kit and c-Fms inhibitor in MPNST cells and xenografts. Although both drugs showed comparable efficacy in vitro, PLX3397 treatment was superior in blocking RTK pathways and resulted in significant macrophage depletion in vivo. PLX3397 and rapamycin combination further enhanced macrophage depletion and resulted in sustained tumor suppression. PLX3397 and rapamycin combination therapy could provide a new therapeutic approach for the treatment of MPNSTs.

Autophagy Inhibition Enhances Efficacy of Epirubicin in TNBC

Chittaranjan et al. Page 3159

Triple negative breast cancer (TNBC) is a heterogenous disease associated with treatment resistance and a lack of effective therapeutic targets. In this study, Chittaranjan and colleagues explore whether manipulating autophagy improves treatment efficacy in TNBC. They find that epirubicin-induced apoptosis was augmented by autophagy suppression in both anthracycline - sensitive and resistant TNBC cells in vitro. In TNBC tumor xenograft mouse models, combined treatment of epirubicin and the autophagy inhibitor hydroxychloroquine significantly reduced the growth of both anthracycline sensitive and resistant TNBC tumors, compared with either monotherapy. These findings support a strategy combining autophagy inhibition with anthracycline therapy for TNBC.

PET/MRI in Primary Prostate Cancer

Hartenbach et al. Page 3244

Reliable detection and characterization of prostate cancer is still challenging. In a registered prospective diagnostic trial, Hartenbach and colleagues investigated the value of combining the high sensitivity of ¹⁸Fluoroethylcholine-(FEC)-PET with the high resolution of T2w endorectal MRI for the detection of primary prostate cancer. They reported significantly higher diagnostic accuracy for the combination of both imaging techniques as compared to each single method in the detection of the clinically significant intraprostatic tumor lesions. Furthermore, FEC-PET enabled noninvasive assessment of tumor aggressiveness in this setting. Combined PET/MRI promises to reduce the number of patients subjected to over- or undertreatment and could potentially enhance the success rate of needle biopsies.