Highlights of This Issue

The majority of alveolar rhabdomyosarcomas (aRMS) are driven by the oncogenic fusion protein PAX3-FOXO1. Novel therapies are needed to target PAX3-FOXO1 or pathways supporting its tumorigenic properties. To this end, Kephart and colleagues conducted a screen for genes that collaborate with PAX3-FOXO1, and identified the secreted Wnt inhibitor SFRP3. Genetic suppression of SFRP3 in aRMS cell lines decreased proliferation and increased apoptosis and differentiation. In a murine xenograft model, suppression of SFRP3 inhibited aRMS tumor growth and sensitized tumors to vincristine, part of the chemotherapeutic backbone of RMS therapy, suggesting that targeting SFRP3 may be a promising therapeutic strategy.

Hong and colleagues conducted a phase I clinical trial of lenvatinib—a multikinase inhibitor of VEGFR 1–3, FGFR 1–3, PDGFRα, RET and KIT—in patients with solid tumors. The maximum tolerated dose was 10 mg twice daily. Drug-related toxicities included hypertension (43%), fatigue (42%), proteinuria (39%), and nausea (25%). Twelve patients (15.6%) achieved partial response (PR, n = 9) or unconfirmed PR (n = 3); 19 (24.7%) achieved stable disease ≥23 weeks. The toxicity profile and antitumor activity of lenvatinib are encouraging.

Little is known about miRNAs in the development and treatment of T-cell lymphoblastic lymphoma (T-LBL). Using microRNA microarrays, Qian and colleagues reported, for the first time, that the downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence. Moreover, in vitro and in vivo studies showed that miR-374b suppressed cell tumorigenicity and promoted cellular apoptosis by inhibiting AKT signal pathway though directly repressing Wnt-16 and AKT1. Targeting miR-374b pathway may represent novel prognostic biomarkers and new therapeutic strategies to improve the therapy and survival of patients with T-LBL.

Cancer-associated fibroblasts (CAFs) have been associated to recurrence and survival in colon cancer. After proteomic characterization, the authors identified LOXL2 as an upregulated protein in purified colon CAFs. High expression of LOXL2 showed a clear association, either disease-free or overall survival in colon cancer patients. In addition, it displayed a significant prognostic value in the stratification of high-risk stage II and III patients. Thus, LOXL2 shows promise as a relevant tool in clinical practice for risk classification, which could lead to a more aggressive therapy and better outcomes for stage II patients.