Editor's choice: Toward precision medicine in glioblastoma: the promise and the challenges

Integrated sequencing strategies have provided a broader understanding of the genomic landscape and molecular classifications of multiple cancer types and have identified various therapeutic opportunities across cancer subsets. Despite pivotal advances in the characterization of genomic alterations in glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. In this review, we highlight potential reasons why targeting single alterations has yielded limited clinical efficacy in glioblastoma, focusing on issues of tumor heterogeneity and pharmacokinetic failure. We outline strategies to address these challenges in applying precision medicine to glioblastoma and the rationale for applying targeted combination therapy approaches that match genomic alterations with compounds accessible to the central nervous system.     

Erythropoietin: the swinging pendulum

Erythropoiesis stimulating agents (ESAs) have been used widely for anemic patients, especially those on dialysis and with cancer. However, reports have suggested shorter survival in erythropoietin (EPO)-treated cancer patients. The purpose of this review is to summarize and evaluate critically the current information about ESA treatment and its possible association with mortality in cancer patients. The pendulum that initially swung in the direction of widespread ESA treatment, and then in the direction of no treatment, is swinging back toward a stable position. This review also provides tools to decide how and when to use ESAs safely, according to accepted guidelines.     

Cancer: defeating the immortal

My first reaction when I was invited to contribute an article for the section "Profiles and Legacies" of Cancer Biology & Therapy was a shock. Am I that old, at the age of 46 years, that I should write my own obituary? But then I realized that I would have the opportunity to share some of my intimate convictions, dilemmas and doubts. So instead of an auto-apotheosis, this piece will simply translate what I could tell a friend during an after-dinner conversation, knowing that the plans for the future (optimistically) outnumber the experiences in the past.     

Metastases: the glycan connection

An association between protein glycosylation and tumorigenesis has been recognized for over 10 years. Associations linking the importance of glycosylation events to tumor biology, especially the progression to metastatic disease, have been noted over many years, Recently, a mouse model in which β1,6-N-acetylglucosaminyltransferase V (a rate-limiting enzyme in the N-glycan pathway) has been knocked out, was used to demonstrate the importance of glycosylation in tumor progression. By crossing mice lacking this enzyme with a transgenic mouse model of metastatic breast cancer, metastatic progression of the disease was dramatically reduced. These experiments provide in vivo evidence for the role of N-linked glycosylation in metastatic breast cancer and have significant implications for the development of new treatment strategies.