Review Articles in 2013

Many targeted anticancer treatments may benefit only a subgroup of the histologically-defined population and thus may be missed by traditional randomized clinical trial designs that focus on the overall treatment effect. New biomarker driven designs can help to identify subgroups of patients who are most likely to benefit from these treatments. In this Review the authors discuss how to select appropriate designs and analysis strategies for phase III, biomarker driven clinical trials, using specific examples to illustrate their advantages (and disadvantages).

Chemoprevention has been increasingly explored to mitigate the global burden of prostate cancer and the overtreatment of indolent disease that has arisen in the prostate-specific antigen screening era. In this Review, the authors summarize the major findings of chemoprevention trials and discuss the future opportunities in this arena.

Is there such a thing as a 'good death'? Palliative care services alleviate the debilitating physical symptoms and psychological distress that patients with cancer frequently experience at the end of their lives. In this Review, Khan and colleagues discuss the preferences of these patients and how advance care planning can help in meeting these choices.

Recent immunotherapy approaches have focused on antibodies that block immune checkpoints, and these approaches have produced significant clinical responses in melanoma, lung cancer and kidney cancer. The authors of this Review briefly review the basic immunology underlying an antitumour immune response, and discuss the most relevant clinical trial results in these three tumour types.

Primary care providers are pivotal in reducing diagnostic delay of cancer, particularly in health systems that have long waiting times for outpatient diagnostic services. In this Review, the authors discuss several aspects of primary care, from referrals to communication and follow-up care, focusing on the most common cancers managed at the GP office.

Diffuse large B-cell lymphoma (DLBCL) is curable in advanced stages, but up to one-third of patients will ultimately fail to respond to initial therapy. As we have now entered the molecular era of defining DLBCL, the goal is to pinpoint driver mutations and pathway addictions within distinct molecular subsets of DLBCL. This Review describes the current molecular understanding of DLBCL and discusses promising targeted approaches for each subtype.

In this Review, the authors describe the pathophysiological effects of chemotherapy and radiotherapy that affect the heart and treatment-related cardiovascular effects in children with cancer. They argue that 5-year event-free oncological survival is no longer the paradigm of successful treatment of childhood cancer; instead overall quality of life is and maximizing oncological efficacy while minimizing toxicity and late-effects should be the ultimate goal.

Biopsy of suspected metastatic lesions is recommended, but not always performed in the clinic. Niikura and colleagues outline the rationale and techniques for performing biopsies on suspected breast metastases. The authors describe the issues surrounding biomarker discordance between primary and metastatic tumours and outline the optimal treatment approach to limit such problems.

Iniparib showed promising results in randomized phase II trials in patients with triple-negative breast cancer; however, negative results from a phase III study in this disease setting, tempered enthusiasm for this agent. The authors of this Review scrutinize the development of iniparib from preclinical studies to registration trials, and identify and discuss the pitfalls in the development of anticancer drugs to prevent future late-stage trial failures.

Establishing breast cancer chemoprevention in standard clinical practice requires advances in many different fields, including biomarker research, the development of more powerful tools to predict and communicate the risks and benefits of treatments and establishing innovative trial designs. In this Review, the authors examine the efforts in breast cancer chemoprevention and explain why the field is progressing slowly than hoped.

Medications commonly used by large populations to treat non-cancerous medical situations are attractive candidates for cancer prevention. This Review discusses three pharmacological agents with chemopreventive potential: statins, metformin and bisphosphonates. The authors outline the pharmacological mechanisms of action of these agents, the supporting clinical evidence for their efficacy and safety in large populations, and discuss how these agents should be used in the ongoing aim of preventing cancer.

Momentum is building for carrying out more phase III comparative trials in gastric cancer, with some using biomarker-based patient selection strategies. In this Review, the authors discuss representative molecular and clinical dimensions of gastric cancer, the fourth most common cancer in men and fifth most common cancer in women.

There are many circumstances where patients respond to reintroduction of the same therapy (drug rechallenge) following relapse or disease progression during therapy, and in a few cases, when a therapy is continued beyond disease progression. The authors comprehensively describe the available data on rechallenge and continuation beyond progression treatment strategies, discuss the potential mechanisms explaining tumour re-sensitization with reintroduced or continued therapy, and make the case for why drug resistance definitions need to be re-evaluated.

Immunotherapy is associated with durable clinical benefit in patients with melanoma, and this consensus statement outlines recommendations for its use. The panel has based their guidance on the available evidence and outlines a treatment paradigm using drugs that are FDA approved.

Advances in the arena of whole-genome sequencing have revealed biomarkers of drug sensitivity and resistance in both renal cell carcinoma and urothelial tumours. This Review article highlights those markers of particular interest and discusses the preclinical and clinical evidence supporting their utility.

Neurofibromatosis type 1 (NF1) and type 2 (NF2) are distinct genetic disorders that are characterized by an increased incidence of tumour development, predominantly affecting the nervous system. The authors discuss the clinical features, genetic aetiologies, and pathogenesis of NF1 and NF2, the current treatment options as well as advances in clinical and preclinical research that will impact on the future treatment of these tumours.

Small bowel adenocarcinomas are rare, histologically diverse tumours and their incidence worldwide is increasing. Despite this, research efforts have received comparatively little attention compared with other cancers with a similar incidence. The authors present an evidence-based approach to present-day management of small bowel adenocarcinoma, describe contemporary challenges and uncover evolving paradigms in the management of these rare neoplasias.

Luminal breast cancer is the most-frequently occurring subtype of breast cancer, but it is a highly heterogeneous disease. Data are emerging to assist in the stratification of patients to the optimal treatment and to address therapy resistance. This Review outlines the biology of this disease, and discusses the treatment options and ongoing studies for women with oestrogen receptor-positive breast cancer.

Optical imaging that exploits invisible near-infrared (NIR) fluorescent light (700–900 nm) has the potential to improve cancer surgery outcomes, minimize anaesthesia time and lower health-care costs via its improved contrast and depth of tissue penetration relative to visible light. This Review introduces the concept of NIR fluorescence imaging and examines imaging system and contrast agent optimization.

Evidence links obesity to increased cancer incidence, and possibly also to poorer cancer survival. Obese patients face a range of specific challenges related to the diagnosis and treatment of cancer. This Review summarizes the available literature addressing the clinical management of obese patients with cancer and discusses opportunities to improve the cancer care of these patients.