Kimbrough et al. Page 4576

Molecular imaging with targeted probes could improve diagnosis, staging, and monitoring of pancreatic ductal adenocarcinoma. Kimbrough and colleagues utilized a novel imaging technology, multispectral optoacoustic tomography, which detects acoustic signals generated by electromagnetic stimulation of probes. Their probe, V7-750, was designed to target acidic extracellular pH and thus improve tumor detection. The V7-750 probe specifically accumulated within pancreatic tumors in mice as compared with pH-insensitive, K7-750 probe, as detected using MSOT, thus demonstrating promise as the basis of a clinically relevant tool in detection of cancer and possible monitoring in patients.

Cui et al. Page 4619

Development of chemoresistance is an underlying cause for the majority of cancer therapy failures. The Notch signaling pathway has potential to promote chemoresistance through its ability to promote survival signals and cancer-like stem cells. To determine if inhibition of Notch signaling diminishes chemoresistance, Cui and colleagues evaluated the adjuvant activity of a γ-secretase inhibitor (GSI) in models of prostate cancer. The GSI enhanced docetaxel-mediated tumor response through inhibiting both cell survival signaling and generation of cancer-like stem cells. These results suggest that Notch pathway inhibition has potential to serve as an adjuvant to extend the effectiveness of chemotherapeutics.

Wang et al. Page 4676

Castration-resistant prostate cancer (CRPC) is a major challenge in prostate cancer treatment, but no effective treatment targeting CRPC is currently available. Wang and colleagues demonstrated the existence and the functional roles of autocrine cholinergic system in prostate cancer. Activation of cholinergic muscarinic receptor 3 (CHRM3) promoted prostate cancer growth and castration resistance. Blockade of CHRM3 by shRNA or selective antagonist darifenacin effectively inhibited prostate cancer growth and castration resistance both in vitro and in vivo. These findings suggest that blockade of CHRM3 may represent a potential adjuvant therapy in prostate cancer treatment.

Della Corte et al. Page 4686

EGFR-TKI resistance represents a major challenge for NSCLC patients' treatment. Because the Hedgehog pathway is an important mediator of epithelial-to-mesenchymal transition, the authors studied Hedgehog signaling activation in preclinical models of EGFR-TKI resistance. SMO gene amplification, concomitantly with MET activation, was identified for the first time as a novel mechanism of EGFR-TKIs' acquired resistance in an EGFR-mutated NSCLC model, supporting the rationale for a combined therapy. Also, in EGFR-wild-type NSCLC models, concomitant inhibition of Hh and EGFR reverts EGFR-TKI resistance. In light of these results, screening of SMO alterations is strongly recommended in NSCLC patients at first progression to EGFR-TKI therapy.