Volume 9 Issue 2, February 2012

Highly clinically relevant ovarian cancer clinical research in 2011 focused on an increased understanding of the biology of the malignancy, limitations of strategies for early detection and screening, and the provocative reports of alternative primary and second-line management strategies.

Options to treat late-stage castration-resistant prostate cancer continued to increase in 2011, as three agents with different mechanisms of action prolonged life and a fourth reduced the morbidity of skeletal metastases. These outcomes contrasted with the heightened controversy generated by the recommendation against PSA screening and other early detection strategies.

2011 saw improvements in our understanding of B-cell malignancies: insights into the genomic basis of chronic lymphocytic leukemia were achieved; reduced treatment intensity caused fewer toxic effects in early-stage Hodgkin lymphoma; first-line rituximab maintenance therapy improved outcome in follicular lymphoma; and selected patients with diffuse large-cell lymphoma benefited from the addition of bortezomib.

Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.

Bone-targeting treatments have transformed the quality of life of patients with metastatic bone disease. 2011 saw the emergence of denosumab—a RANK ligand-specific antibody—as a more-effective alternative treatment to bisphosphonates and of data on the use of bone-targeting treatments to prevent metastasis from breast and prostate cancers.

Rates of central nervous system (CNS) involvement in metastatic cancer are believed to be increasing. The neurosurgical treatment of patients with metastatic cancer is an integral component of multimodality therapy for brain and spinal metastases. This Review discusses data from current randomized clinical trials that examine the role of neurosurgical intervention in the treatment of patients with CNS metastases.

This Review discusses recent evidence that indicates that different genetic alterations might be related to distinct sensitivity to targeted therapies. It examines prototypical examples and asks what is the role of cancer mutations as predictors of sensitivity and resistance to targeted therapies? Further, what are the implications for the 'personalized' treatment of cancer patients?

This Review article approaches the area of targeted therapies from two angles: efficacy and side effects. The authors outline the successes that have been achieved in treating cancer with targeted therapies and also discuss the pitfalls and quality of life issues that still need to be addressed.

Recent phase III trials of denosumab, a monoclonal antibody that inhibits RANKL, have demonstrated superiority over zoledronic acid in reducing skeletal morbidity in patients with metastatic bone disease. Brown and Coleman describe the emerging role of denosumab in maintaining bone health in the oncology setting and discuss the factors to consider when deciding whether to use bisphosphonates or denosumab in clinical practice.

Since the issue of the seventh edition of the TNM classification guidelines for colorectal cancer there has been discussion about some of the associated changes in classification and stage. This Perspectives article examines the impact a new staging system can have on patient care, and makes suggestions for how the constant re-evaluation of classification guidelines could be improved going forward.