Volume 11 Issue 11, November 2014

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.

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.

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.

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.

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.

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.

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?

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.

November 2014 marks the 10th anniversary of the launch of Nature Reviews Clinical Oncology, originally published under the title ofNature Clinical Practice Oncology. To celebrate this milestone, we have commissioned a collection of Decade in Review articles from key opinion leaders to summarize the major advances in six sub-specialties of oncology over the past 10 years. We also present a comprehensive Perspectives article that summarizes the key advances and challenges in translational oncology. In addition, we have commissioned a Viewpoint article in which we asked four of our Advisory Board members from around the globe to discuss topics such as clinical development and testing of multiple agents in combination, regulatory challenges relating to drug development and trial design, and funding for basic research. Together, these articles provide an authoritative snapshot of the oncology field in 2014, and how this might progress over the forthcoming decade. These articles, together with a special infographic,provides a snapshot of 10 years of the journal in numbers.