Inhibition of Pol I and PIM in Advanced Prostate Cancer
Metastatic castrate-resistant prostate cancer (mCRPC) is the most aggressive and incurable stage of the disease and the MYC oncogene is almost universally overexpressed in mCRPC. MYC directly enhances RNA polymerase I (Pol I) transcriptional activity but also regulates and cooperates with PIM kinases to accelerate tumorigenesis. Rebello and colleagues demonstrate the preclinical efficacy of targeted therapy against Pol I in combination with pan-PIM inhibition in genetically engineered mouse models and in patient-derived xenografts. This combination strategy shows promising efficacy in inhibiting MYC-driven prostate cancer and has implications for treating castrate resistant disease.
Inflammatory Infiltrates in Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. In this study, Feldmeyer and colleagues performed immune profiling of T-cell infiltration and PD-1/PD-L1 expression in primary MCC and related them to patient outcomes and Merkel cell polyomavirus (MCPyV) status. CD3+ and CD8+ T-cell density at the tumor periphery associated with improved overall survival for MCPyV+ MCC. The findings provide a potential biomarker for risk stratification and prognosis for MCC and a rationale to use immune checkpoint inhibitor therapy.
Significance of TP53 mutation in Anaplastic Wilms Tumor
Anaplasia in Wilms tumor has been associated with TP53 mutations. Ooms and colleagues show that 41% of prospectively identified diffuse anaplastic Wilms tumor (DAWT) tissue lacks TP53 abnormalities. TP53 wild type expression was associated with no or a very low volume of anaplastic cells in the tumor and significantly lowered the relapse rate. There may be a subset of DAWT patients without TP53 abnormalities that do better and may require less-intensive toxic therapy in some children.
F. Nucleatum and Prognosis in Esophageal Cancer
F. nucleatum primarily inhabits the oral cavity and can cause periodontal disease. Yamamura and colleagues demonstrate the presence of F. nucleatum in esophageal cancer tissue that was associated with tumor stage and poor prognosis. They additionally show a correlation with F. nucleatum and aggressive tumor behavior through activation of chemokines like CCL20. The data suggest that F. nucleatum could be used as a prognostic biomarker for esophageal cancer.
- ©2016 American Association for Cancer Research.