Reviews & Analysis

A key challenge in oncology is obtaining drugs predicted to be beneficial based on the patient's tumour profile. One solution is creation of a national facilitated access programme and registry for off-label use of targeted anti-cancer drugs. Schilsky discusses several key elements of implementing personalized cancer care services in an oncology practice setting and offers solutions to some of the obstacles of making personalized medicine available to many patients.

There is much concern in the literature over the lack of reproducibility of many scientific reports. In this Perspective, the authors discuss how cognitive biases in research and flaws in the academic incentive system also contribute to the publication of immature results. The authors suggest some changes to the grant submission and funding system that could further improve the reproducibility of research findings.

In this Perspectives article, the authors propose that lower histological grade in breast cancer might be a hallmark of relative chromosomal stability, which in turn might be predictive of additional benefit from taxane-based chemotherapy in women with oestrogen-receptor-positive cancer. They interpret published data to on the relationships between tumour grade, chromosomal instability and intratumour heterogeneity and discuss the potential use of chromosomal instability to tailor therapy.

The majority of patients with cancer do not die as a result of the primary tumour, rather from the metastases that arise from that tumour. The mechanisms and markers of metastasis have, therefore, been a main focus of both clinical and preclinical research. This Perspectives article discusses the hurdles that need to be overcome to successfully translate the preclinical metastasis research into the clinic.

In terms of drug development, the main driving force should be optimized benefit–risk to patients; however, no drug can be of real benefit unless it has achieved approval from the regulatory agencies. This Perspectives allows us a peek behind the door of one of those agencies (EMA) and outlines the hurdles that exist and that need to be overcome before we can have an efficient, biomarker-driven drug development program. Points for discussion in the community are raised and suggestions are put forward.

Antiangiogenic therapies have secured a role in the treatment of multiple cancers. However, the success of this targeted therapy is not as great as originally anticipated. In this Perspectives article, the authors use data from clinical trials to uncover where some of the problems with this therapy lie, discuss exciting recently published data and look to what the next steps should be.

The increasing reliance on hazard ratios for the assessment of clinical trial data prompted this Perspectives article, designed to outline the uses and misuses of this popular statistical value. The authors use real trial data and synthetic examples to explain how the hazard ratio is derived and why the numerical value of a survival measure should also be published alongside it.

Randomized controlled trials (RCTs) pose dilemmas in terms of the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise is often regarded as a solution to this problem. The authors critically evaluate clinical equipoise and highlight its flaws as an ethical requirement for RCTs and propose an alternative method of risk–benefit assessment.

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.