Volume 8 Issue 6, June 2011

Does targeting VEGF improve the lives of patients with metastatic breast cancer? Since the E2100 trial, there has been uncertainty about the benefit and toxicities of anti-VEGF therapy. By evaluating the RIBBON-1 trial results, we ask is such therapy failing, and are we considering all variables when scrutinizing the data?

Outcomes in patients with peripheral T-cell lymphomas are poor and there are no established standards of care for patients in the relapsed and refractory setting, owing in part to the lack of multicenter, controlled clinical trials. Recently, encouraging results were reported in this setting with pralatrexate—a novel folate analog.

Zoledronic acid is a potent bisphosphonate used as the standard therapy for the prevention of skeletal-related events in patients with solid tumors metastatic to bone. Three phase III studies have reported head-to-head comparisons of zoledronic acid with denosumab, an inhibitor of the RANK signaling pathway.

The treatment of microscopic metastatic disease is based on the assumption that micrometastases and overt metastases will respond to the same interventions; however, clinical observations illustrate this assumption is incorrect. The authors discuss our existing understanding of the metastatic cascade, emerging therapeutic targets involved in the metastatic process, and how novel anti-metastatic therapies might be developed for clinical use.

Metastasis-suppressor genes (MSGs) are involved in diverse molecular processes in multiple tumor types; therefore, treatment strategies based on MSGs have unparalleled potential to improve patient care. In this Review, barriers specific to the translation of MSG biology into clinical practice are discussed and future research directions necessary for clinical advances are delineated.

Brain metastases remain a serious obstacle in the successful treatment of patients with solid tumors. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients.

Metastatic bone disease in advanced-stage prostate cancer causes some of the most distressing symptoms and is associated with poor survival. This Review discusses the complex pathology of the bone lesion in metastatic prostate cancer and promising therapeutic strategies to treat this disease.

The self-seeding model provides a new paradigm whereby progression from a primary tumor to metastasis is understood as a multidirectional process, balanced between mitotic (primary tumor), seeding (metastasis) and self-seeding processes. The authors discuss how this model helps to explain various enigmas including the similarities between pre-neoplasia and invasive cancer, mammographic breast density as a risk factor, and the relationship between local control and distant recurrence.

This Perspectives article expands on the previously proposed clinical state of metastasis termed 'oligometastases' that refers to restricted tumor metastatic capacity. The authors outline the concept, discuss the evidence and the treatment implications and go on to describe ongoing studies in the field.

Nature Reviews Clinical Oncologyfeatures a Focus on metastasis in the June and July 2011 issues. This focus features discussions of the recent breakthroughs in knowledge of the mechanisms and treatment of metastasis by key opinion leaders in the field. Topics include tumor self-seeding, metastasis-suppressor genes, bone metastasis, brain metastasis and oligometastases. The web page for this focus issue also includes links to related articles from across Nature Publishing Group to provide more background information on this topic.