Highlights of This Issue

Abstract

ENMD-2076 is a novel, orally bioavailable multitargeted antiangiogenic and Aurora kinase inhibitor with preclinical activity against multiple cancer types. In this study, Tentler and colleagues examined the efficacy of ENMD-2076 in vivo against primary and cell line–derived murine xenograft models of colorectal cancer (CRC). They used tumor growth inhibition, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and 18FDGpositron emission tomography (18FDG-PET) to assess the antiproliferative, antiangiogenic, and antimetabolic responses to ENMD-2076, respectively. They found that ENMD-2076 demonstrated robust antitumor activity against cell line and patient-derived xenograft models of CRC, supporting further clinical investigation of this agent in CRC.DNA damage responses and telomere integrity represent anticancer barriers, as they prevent genome instability and occurrence of new genomic abnormalities. Lantuejoul and colleagues describe the chronology of telomere machinery during both bronchial and bronchioloalveolar carcinogenesis. They report increased expression of telomeric maintenance proteins TRF1 and TRF2 and of DNA damage response (DDR) proteins, which were progressively activated from low- to high-grade dysplasia, and from atypical adenomatous hyperplasia to in situ adenocarcinoma. The DDR proteins became impaired in invasive squamous cell carcinoma and adenocarcinoma, suggesting they could represent predictive factors for cancer progression and potential markers of drug sensitivity.The high recurrence rate of low-grade non–muscle-invasive bladder tumors necessitates frequent cystoscopic monitoring of patients. FGFR3 mutations are associated with prognosis, and surveillance with FGFR3 mutation detection in voided urine could ultimately reduce the number of cystoscopies and improve patient quality of life. Here, Zuiverloon and colleagues determined the recurrence risk associated with urine positive for an FGFR3 mutation, and the predictive value of consecutive FGFR3-positive urine samples over time. Their findings suggest that having FGFR3-positive urine is associated with a four-fold higher recurrence risk, and that an individualized surveillance protocol based on FGFR3 detection should be feasible.In this study, Armstrong and colleagues report giving a short course of the mTOR inhibitor rapamycin to men with localized prostate cancer prior to radical prostatectomy. They found that the activity of the downstream mTOR target S6 was inhibited in the majority of tumors. However, there was no change in measures of tumor apoptosis or proliferation, despite a reduction in p27 nuclear localization and no detectable increase in Akt activation. While an antiangiogenic or novel antitumor mechanism of action for rapamycin cannot be excluded, these findings suggest that single agent mTOR inhibition may be insufficient to impact on prostate tumor growth or survival.