Review Articles in 2011

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.

Gene-expression profiling has led to the development of signatures designed to predict survival and treatment response in patients with breast cancer. In this Review, Prat et al. discuss the clinical utility of gene-expression-based assays and compare them with the performance of breast cancer biomarkers that are currently used as standard of care.

If a targeted therapy demonstrates convincing efficacy in early clinical testing, can randomized phase III trials be avoided? Sharma and Schilsky discuss when it is reasonable to consider foregoing randomized phase III trials before drug approval and also highlight the caveats. They explore the consequences of such an approach and propose criteria that the drugs must meet to be approved without a phase III trial.

Although breast density is a powerful factor for predicting the risk of developing breast cancer, unfortunately current methods of measuring mammographic density are not entirely satisfactory. This Review analyzes the different factors affecting breast density and how to consider them so that the accuracy of individual risk assessments can be improved.

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.

Despite the advent of HER2-directed therapies, many patients with HER2-positive early stage breast cancer relapse and die of this disease. Trials to define, refine and optimize the use of the approved HER2-targeted agents are ongoing. New approaches are being developed and a series of large trials in the adjuvant and neoadjuvant settings are planned or in progress. In this Review, Arteaga et al. describe the current treatment for HER2-positive breast cancer and provide an update on ongoing clinical trials and translational research.

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?

The size, length and cost of phase III clinical trials are prompting oncology researchers and pharmaceutical companies to look for other options. This Review outlines adaptive clinical trial designs that can address many questions at once. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same study and are matched with their biomarker signatures.

Radioimmunotherapy is being used successfully for the treatment of patients with hematological malignancies, however similar efficacy is lacking in patients with solid tumors. Pouget and colleagues explain basic concepts of radiobiology, review the results of clinical radioimmunotherapy trials, and highlight potential strategies to improve the efficacy of radioimmunotherapy in patients with solid tumors.

Carcinomas of an unknown primary origin (CUP) are histologically confirmed metastases for which a primary tumor could not be found despite an extensive diagnostic workup of the patient. The authors of this Review discuss the clinical evaluation of patients with CUP, describe how to identify specific CUP subsets, and outline treatment strategies and outcomes of patients with CUP.

Many trials report progression-free survival rather than overall survival outcomes but few trials have good quality-of-life data collected via patient-reported outcome measures. The authors describe what is understood by progression-free survival, and discuss what this means for patients with advanced-stage cancer and what factors should be taken into account when clinicians try to help patients considering treatment options.

The ability to follow the distribution and migration of biologically active cells in living organisms is crucial for the development of cell-based therapies. In this Review, Kircher et al. describe the imaging principles underlying currently available cell-tracking methods and highlight recent examples of their application in animal models and patients.

Personalized medicine in lung cancer has seen great advances in the past decade. In this Review, Tony Mok examines the development of drugs that target mutations inEGFR and the oncogenic fusion gene EML4–ALKas examples of this progress and discusses the necessary tools to improve the chance of future successes.

Personalized cancer medicine—where treatments are selected and tailored for individual patients—is now a reality, although improvements are needed to identify predictive biomarkers for stratifying and subgrouping patients. A critical appraisal of biomarkers in clinical use for a range of cancers is presented, and the unique and unprecedented opportunity to deliver personalized cancer therapy on an ongoing and rational basis is highlighted.

Current treatments for patients with locally advanced rectal cancer (LARC) consist of neoadjuvant chemoradiotherapy, followed by total mesorectal excision and adjuvant chemotherapy. Aklilu and Eng review the pivotal trials that have led to this treatment paradigm and discuss novel therapies that are being developed for patients with LARC.

Cancer immunology is an interactive field that requires the skills of oncologists and immunologists, in addition to other aspects, such as pathology. This Review uses colorectal cancer as a prototypical cancer and describes how molecular features and immune reactions are inter-related.

Treatment options for patients with castration-resistant prostate cancer are rapidly increasing, offering these patients hope of better quality of life and longer disease-free periods. This Review discusses the recent advances, the pitfalls and outlines a new treatment paradigm for the future.

Hormone replacement therapy (HRT) has been linked by several reports to an increased risk of breast cancer. The precipitous decrease in breast cancer incidence shortly after the cessation of HRT is well established. In this Review, Steven Narod summarizes the evidence and asks the question, where do the breast cancers go?

The adoptive transfer of autologous tumor-infiltrating lymphocytes is one of the most promising developments of recent years for the treatment of patients with solid tumors. In this Review, a pioneer of this method, Steven Rosenberg, outlines the history and current situation for this therapy and explains what clinicians need to know.

Radiation therapy techniques have made great strides over the past decade, both in terms of efficacy and in the avoidance of the associated toxic effects. This Review highlights the particular areas of concern for patients with head and neck cancer and outlines how to avoid toxic effects, while maintaining the optimal treatment efficacy.