Tumour biology: herceptin acts as an anti-angiogenic cocktail

Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.     

Pathology: cancer cells compress intratumour vessels

The delivery of therapeutic drugs to solid tumours may be impaired by structural and functional abnormalities in blood and lymphatic vessels. Here we provide evidence that proliferating cancer cells cause intratumour vessels to compress and collapse. By reducing this compressive mechanical force and opening vessels, cytotoxic cancer treatments have the potential to increase blood perfusion, thereby improving drug delivery.     

Cooper instability of composite fermions

When confined to two dimensions and exposed to a strong magnetic field, electrons screen the Coulomb interaction in a topological fashion; they capture an even number of quantum vortices and transform into particles called 'composite fermions' (refs 1-3). The fractional quantum Hall effect occurs in such a system when the ratio (or 'filling factor, nu) of the number of electrons and the degeneracy of their spin-split energy states (the Landau levels) takes on particular values. The Landau level filling nu = 1/2 corresponds to a metallic state in which the composite fermions form a gapless Fermi sea. But for nu = 5/2, a fractional quantum Hall effect is observed instead; this unexpected result is the subject of considerable debate and controversy. Here we investigate the difference between these states by considering the theoretical problem of two composite fermions on top of a fully polarized Fermi sea of composite fermions. We find that they undergo Cooper pairing to form a p-wave bound state at nu = 5/2, but not at nu = 1/2. In effect, the repulsive Coulomb interaction between electrons is overscreened in the nu = 5/2 state by the formation of composite fermions, resulting in a weak, attractive interaction.     

Angiogenesis in cancer and other diseases

Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases. Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti-angiogenic molecules, some of which are already in clinical trials. The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated. This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed.     

Molecular mechanisms and clinical applications of angiogenesis

Blood vessels deliver oxygen and nutrients to every part of the body, but also nourish diseases such as cancer. Over the past decade, our understanding of the molecular mechanisms of angiogenesis (blood vessel growth) has increased at an explosive rate and has led to the approval of anti-angiogenic drugs for cancer and eye diseases. So far, hundreds of thousands of patients have benefited from blockers of the angiogenic protein vascular endothelial growth factor, but limited efficacy and resistance remain outstanding problems. Recent preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies.