Opinion in 2011

The advent of prophylactic mastectomy and the new surgical techniques that are available has encouraged the use of nipple-sparing mastectomy. This Perspectives article examines this technique in terms of aesthetics, contraindications, side effects and recurrence, and outlines why, in the authors' opinion, nipple-sparing mastectomy should be offered to patients with breast cancer and those at high risk.

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.

The use of therapy that is truly targeted to the needs and biological requirements of an individual patient is an aim for many in the oncology field. Jackson and Sood discuss the implications of targeted therapies on patients and the health-care system and discuss methods that might be used to maximize efficiency, cost effectiveness and patient survival.

Microarray-based gene-expression profiling has advanced the breast cancer field. However, definitive answers to many of the questions for the successful implementation of personalized medicine remain elusive. The authors discuss the hurdles in the development and validation of molecular classification systems, and the challenges ahead for development of the next generation of molecular predictors.

Recent clinical trials aim to identify biomarkers of response and resistance to the agents under investigation. This can require tissue samples that will not necessarily provide a direct benefit to the patient. Given the risks associated with any procedure, not every patient is willing to undergo a research biopsy. In this article, Olson et al. present the rationale to establish when research biopsies should be mandatory and to ensure that clinical trials are designed with scientific and ethical rigor.

Phase I trials have evolved from simple dose-finding studies to studies that provide therapeutic opportunities for patients where no standard therapy is available; however, various factors have hampered patient recruitment on phase I trials. The authors discuss how matching patients with specific genetic aberrations to specific therapies will improve drug attrition rates and improve patient outcomes.

Patients with metastatic disease are usually treated initially with systemic therapy alone. Morgan and Parker review clinical data suggesting that the local treatment of the primary tumor might retard progression of distant metastases, making the case for the conduct of more randomized clinical trials that investigate this hypothesis.

Many patients with soft-tissue sarcomas are treated with doxorubicin-based adjuvant chemotherapy, but whether this therapy translates into a survival benefit is controversial. The authors of this Perspectives article critically analyze available clinical data and discuss the implications of these data on current and future treatment efforts.

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.

The authors takes a systems-biology approach to the problems of personalized cancer medicine. They describe the challenges of moving to a discipline that is predictive, personalized, preventive and participatory and explore methods for overcoming these obstacles.

Modern challenges in oncology, in particular the advent of targeted therapies and personalized medicine, highlight the need for developing a consortium of comprehensive cancer centers to run clinical trials in rare, molecularly-defined populations, and implement high-throughput technologies for daily practice.

A number of biomarkers that predict clinical outcome in response to gemcitabine treatment have been identified. These markers could be used in the clinic to personalize treatment, thereby improving efficacy and reducing adverse effects. The authors of this article describe how treatment can be tailored according to the pharmacogenetics and pharmacokinetics of each patient. In particular, evaluating the status of the liver enzyme cytidine deaminase holds promise as a strategy to optimize therapy.

In this Perspective, the clinical disappointment of mitosis-specific agents is explained in the context of the mechanism of action of microtubule-targeting agents. The authors propose a new paradigm for the anticancer activity of microtubule-targeting agents and suggest that mitosis-specific inhibitors will not result in significant clinical impact.