Highlights of This Issue

Abstract

Therapies targeting the phosphoinositide 3-kinase (PI3K) pathway are currently in clinical development. Cancers with oncogenic PIK3CA mutations may be particularly susceptible to these agents, and improved methods for identifying these mutations from patient samples are needed. Higgins and colleagues evaluated the feasibility of a novel technology called BEAMing to assess PIK3CA mutation status by using blood from patients with metastatic breast cancer. They discovered that BEAMing can reliably detect PIK3CA mutations from blood, and that PIK3CA mutation status can change between primary breast tumors and distant recurrent metastatic disease. Thus, BEAMing shows great potential as a companion diagnostic for future targeted therapies.Metabolic aberrations are increasingly used in cancer diagnostics. To investigate the genetic alterations contributing to low citrate and high choline concentrations in prostate cancer, Bertilsson and colleagues integrated data from transcription and metabolic profiling. Fresh frozen samples from radical prostatectomy specimens were histologically evaluated before high-resolution magic angle spinning and subsequent genome-wide transcription analysis for each sample. The authors found significant covarations between key regulatory enzymes (ACLY, ACON) and citrate as well as for the rise in choline (PLA2G7, CHKA). Their results indicate that these gene products deserve attention as possible targets for prostate cancer-specific therapy.Dysfunctional telomeres are a driving force of genomic instability, which is a hallmark of cancer. Determining telomere dysfunction is one way of monitoring genomic instability. Gadji and colleagues used quantitative 3-dimensional (3D) nuclear imaging and analysis of telomeres to define 3D telomere profiles of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). These profiles consist of quantitative measurements of telomeric length, telomere numbers/nucleus, presence of telomeric aggregates, nuclear volumes, and overall distribution of telomeres in the nucleus. Based on these telomere profiles, the authors stratified MDS and AML patients into subgroups of 9 and 6 patients each, respectively. Furthermore, they propose a chronologic evolution of 3D telomere dysfunction from early-to late-stage MDS and finally transformation to AML.After treatment of tumors with vascular disrupting agents (VDA), systemic mobilization of bone marrow-derived circulating endothelial progenitor cells (CEPC) contributes to revascularization of a viable tumor rim. Nathan and colleagues designed a first clinical trial combining a VDA, combretastatin A4 phosphate (CA4P), with the humanized anti-VEGF-A monoclonal antibody bevacizumab. In patients with advanced solid tumors, disruption of the VDA-induced CEPC spike by bevacizumab resulted in marked reductions in tumor rim size and blood flow as well as enhanced VDA antitumor activity. The combination of VDAs with antiangiogenic agents shows promise in enhancing clinical efficacy of antivascular therapy.