Reviews & Analysis

Recent studies of neuroblastoma have shed light on the dramatic heterogeneity in its clinical behaviour, which spans from spontaneous regression or differentiation to relentless disease progression. This Review describes the different mechanisms of spontaneous neuroblastoma regression—including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation—and the consequent therapeutic approaches, as a better understanding of these mechanisms might help to identify optimal therapies.

Over the past decade, funding for cancer research by the US government—and others—has stagnated, while the demand for investment has grown because of the increasing cancer incidence worldwide. We discuss how National Cancer Institute funding efforts have developed during this period, and the contemporary and future impact of these measures on cancer research in the USA.

It has been a decade of remarkable progress in the field of haematological malignancies with the rapid translation of basic science discoveries into effective targeted therapies. We discuss the most exciting advances in this field, many of which have already produced meaningful improvements in survival and quality of life of patients.

By November 2004, when the first issue of Nature Reviews Clinical Oncology was published, cancer immunotherapy had been successfully applied to the treatment of selected human cancers; however, dramatic progress in the following decade has moved immunotherapy from the sidelines of cancer treatment into the mainstream of modern oncology.

Many cancers, particularly those that arise in childhood, have a hereditary component. In this Perspectives article, the authors provide their views on how the increased adoption of high-throughput DNA sequencing technologies, which produce vast genetic data that is not necessarily limited to known cancer-susceptibility loci, and cancer surveillance strategies are influencing the clinical management of familial cancer. Important ethical issues relating to genetic counselling and disclosure of genetic information on disease susceptibility are discussed, and strategies for approaching these ethical dilemmas are proposed.

Over the past decade, there have been profound shifts in clinical trial design. Phase II randomized studies, phase II/III and other adaptive designs, early surrogate end points, and prospective biomarker-based patient selection have all increased in popularity. We discuss these shifts in clinical trial designs that have increased efficiency in identifying which patients will benefit from specific treatments.

The rise of targeted therapy for solid tumours over the past decade has yielded a cornucopia of novel agents across an array of cancers. Amidst multiple acclaimed successes, targeted therapies are associated with considerable toxicity, and durable responses are often thwarted by genomic chaos driving the evolution of resistant clones; key examples of successes in solid tumours are highlighted herein.

Over the past decade, genetic testing for rare inherited mutations, such as BRCA1 and BRCA2 mutations, has been successfully incorporated into clinical practice. Next-generation sequencing of cancer-susceptibility genes and entire tumour genomes has transformed cancer care and prevention. The discoveries of new cancer syndromes have raised exciting opportunities and potential liabilities for cancer-care providers seeking to incorporate genomic approaches into preventive oncology practice.

Advancement of an investigational therapy into the adjuvant and/or neoadjuvant settings without clear evidence of efficacy in metastatic disease is exceptional; however, this course is being followed in the clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors, owing to their potential benefit for a well-defined subset of patients with tumours defective in homologous recombination. This Review provides a bench-to-bedside overview of PARP inhibitor therapy, and an update on the current status of the clinical development of such agents.

The landscape of translational oncology has shifted dramatically over the past 10 years, characterized by the introduction of more-sophisticated molecular tools into the clinic and advances are being employed in genomic clinical trials that will examine the feasibility of matching a broad range of systemic therapies to specific molecular tumour characteristics. The authors review selected developments in translational cancer biology, diagnostics, and therapeutics that have occurred over the past decade and offer our thoughts on future prospects for the next few years.

Immunoconjugates are specific, effective, minimally toxic anticancer therapies. They allow the delivery of a range of different effectors, including pharmacologic agents, radioisotopes, and toxins, to cancer cells. Of note, highly cytotoxic anticancer molecules could be linked to specific antibodies, which mask the toxic effects of the drug until it reaches its target. This Review summarizes the successes and shortcomings of immunoconjugates, and discusses the future potential for these therapies.

In this Viewpoint, four of our Advisory Board members discuss the key challenges in clinical cancer research that need to be overcome to achieve tangible progress in the next decade. The issues and challenges include clinical development and testing of multiple agents in combination, design of clinical trials, tumour heterogeneity, drug development and trial design, and funding for cancer research. What have we learnt over the past 10 years and how should we progress in the next decade?

In this Viewpoint, four key opinion leaders discuss the slow rate of drug development in paediatric oncology, which must be addressed in a meaningful way if we are to make progress. They discuss a range of aspects, from clinical trial design and biomarker discovery to regulatory amendments and input from industry, government, academia, non-governmental organizations and patient advocacy groups.

Several clinical trials have investigated the antitumour effect of bisphosphonates when used as adjuvant treatment for early stage breast cancer. Among these, the results of the AZURE trial, although negative, highlight the potential benefit of treatment with zoledronic acid in postmenopausal women with high-risk early stage breast cancer.

The cancer community is deeply concerned about the unintended consequences of the current wording of the European Union (EU) draft Regulation on Data Protection, which may challenge the survival of retrospective clinical research, biobanking, and population-based cancer registries in the EU. This directive could negatively affect Europe's competitiveness in cancer research.

Delirium is a common neurocognitive manifestation in patients with cancer, particularly at advanced stages of the disease, and represents a considerable challenge for the patients, their families as well as health-care professionals involved in their care. This Review provides a comprehensive overview of the diagnosis, assessment, pathogenesis and management of delirium. The experiential impacts of delirium on patients with the condition, their family members and health-care practitioners are also discussed.

Lymphoma represents a heterogeneous disease both across and within histological subtypes. The future for the treatment of patients with lymphoma will involve matching a targeted therapy to the unique genetic and molecular composition of each lymphoma. This Review discusses biomarkers that can guide treatment decisions for patients with lymphoma, and explore the challenges and strategies for making biomarker-driven personalized medicine a reality in the cure and management of this disease.

Antiangiogenic therapies are cytostatic rather than cytotoxic and, therefore, do not simply decrease tumour sizes. Thus, traditional assessment of radiographic response according to MRI-based tumour-volume criteria can no longer be considered adequate. Instead, vessel-calibre MRI has emerged as a potential alternative—providing insight into vessel type and oxygenation status, and opening possibilities for clinical trial design and monitoring therapeutic response and outcomes.

Recent advances in multimodality imaging in cancer have involved the integration of multiple quantitative, functional measurements that provide a more-comprehensive characterization of tumours. In this Review, Yankeelov and colleagues discuss how, although some of these approaches still need some adjusting, they can already be applied informatively in clinical trials of cancer therapeutics using existing tools.

Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion. Among the biological mechanisms underlying cancer-related fatigue, inflammation processes have a key role in the development and persistence of this symptom. In addition, genetic, biological, psychosocial, and behavioural risk factors are also associated with the occurrence of cancer-related fatigue. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue.