Highlights of This Issue

Abstract

Administration of recombinant human erythropoietin (rHuEPO) has largely replaced bloodtransfusion in patients with cancer-induced anemia. Potential detrimental effects of thisapproach, such as thromboembolic risks and potential tumor response leading to enhanced disease progression, have become points of discussion and concern. Hedley and colleagues present data demonstrating potentiating effects on metastasis and reduction of chemotherapeutic efficacy in secondary sites by rHuEPO. This study begins to uncover the underlying functional explanation for the adverse events and decreased survival that have been observed in erythropoietin-treated metastatic breast cancer patients undergoing chemotherapy.Cancer-initiating cells (CIC) are being readily identified by elevated levels of aldehyde dehydrogenase (ALDH), namely ALDH1A1, a tumorassociated antigen recognized by HLA class I—restricted CD8+ T cells. Pertinent to developing immunotherapy for targeting CICs, Visus and colleagues demonstrate that ALDHbright cells are sensitive to cytolysis by ALDH1A1-specific CTLs in vitro and in vivo. In preclinical models of human tumor xenografts growing in immunodeficient mice, adoptive therapy with ALDH1A1-specific CD8+ T cells targeted ALDHbright cells and inhibited xenograft growth and metastasis or prolonged survival. These results highlight ALDH1A1 as a target of T cell—based immunotherapy to eliminate CICs.Androgen withdrawal therapy (AWT) is considered the standard of care for patients withmetastatic prostate cancer, but resistance to this therapy develops within 2 to 3 years after treatment. Chen and colleagues show that during AWT, increased levels of the receptor tyrosine kinases HER2 and ErbB3, members of the epidermal growth factor receptor (EGFR)family, result in a significant ErbB-dependent survival advantage that allows progressionto castrationresistant prostate cancer. However, dual EGFR/HER2 inhibition, which alsoinhibits their dimerization partner, ErbB3, induced apoptosis in cells undergoing AWT. Theseresults indicate that administration of dual EGFR/HER2 inhibitors together with AWT may impede the onset of castration-resistant prostate cancer.MicroRNAs (miRNAs) have critical functions across various biologic processes and can be potentially used as cancer biomarkers. Colorectal cancer is a heterogeneous disease, and the identification of various types of colorectal cancer with histopathologic methods alone is challenging. In this study, Balaguer and colleagues used miRNA expression profiling for molecular classification of hereditary and sporadic forms of colorectal cancer. Their data show that miRNA expression profiling not only distinguished between tumor and normal tissues, but more importantly, a subset of miRNAs successfully discriminated among Lynch syndrome, sporadic microsatelliteunstable, and microsatellite-stable colorectal cancers. These findings could have tremendous clinical and translational relevance in the diagnosis, prognosis, and treatment strategy for patients with different subtypes of colorectal cancer.