Highlights of This Issue

Abstract

The combination of bevacizumab, an anti-VEGF monoclonal antibody, with cytotoxic chemotherapy has shown improved progression-free survival in breast carcinoma. However, there is a need to develop biomarkers that can identify patients most likely to benefit from this therapy. Here, Jubb and colleagues examined a large panel of in situ biomarkers in archival tissue from patients enrolled in a phase 3 clinical trial of bevacizumab in breast cancer. Their findings suggest that expression of delta-like ligand 4, neuropilin-1, and VEGF-C may predict progression-free survival benefit from the addition of bevacizumab to capecitabine. Therefore, these biomarkers may aid in patient selection.Organic anion transporting polypeptides (OATPs) are broad specificity transmembrane uptake transporters. Using recently generated Oatp1a/1b cluster knockout mice, Van de Steeg and colleagues studied the role of Oatp1a/1b transporters in drug disposition. They found that Oatp1a/1b transporters play an important role in the in vivo pharmacokinetics of the hydrophobic anticancer drug paclitaxel, mainly by mediating its hepatic uptake. The impact of Oatp1a/1b transporters on the disposition of paclitaxel was unexpected as this drug was thought to mainly pass membranes by passive diffusion. These findings suggest that alterations in tumor or hepatic OATP activity might affect the therapeutic efficacy of paclitaxel.Breast cancer subtypes display characteristic and biologically meaningful gene expression profiles. Here, Graham and colleagues investigated gene expression profiles in histologically normal breast epithelium (NlEpi) microdissected from breasts with either ER+ or ER- breast cancers. They then compared these NlEpi profiles with profiles of ER+ and ER- cancers in 4 external datasets, and found that gene expression in each type of NlEpi resembled gene expression of the corresponding type of invasive breast cancer (i.e., ER+ or ER-). Thus, NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early events in cancer development and locate targets for prevention and therapy.Hereditary head and neck paragangliomas (HNPGL) are associated with mutations in the SDHD (PGL1), SDHC (PGL3), and SDHB (PGL4) genes encoding succinate dehydrogenase subunits. Recently, mutations in the human SDHAF2 gene were described, and this gene was shown to be the ‘imprinted’ PGL2-gene. Here, Kunst and colleagues describe a new branch of the Dutch SDHAF2 (PLG2-SDH5) family and establish the SDHAF2-mutation status of PGL2-family members. The identification of the SDHAF2-mutation provides a useful aid in screening for HNPGL, and the phenotypic characterization of this SDHAF2 (PLG2-SDH5) family is valuable for future counseling of patients and families.