Review Articles in 2014

This Review explores breakthroughs in our understanding and treatment of acquired resistance to tyrosine kinase inhibitors in key molecular subtypes of non-small-cell lung cancer, which may be relevant across multiple different solid malignancies with oncogene-addicted subtypes. The potential of a number of clinical approaches to treat acquired resistance, from new drugs or drug combinations through to the use of more traditional therapies such as radiation or cytotoxic chemotherapy, are highlighted, and the implications for major changes in conducting clinical research in this setting are discussed.

Graft-versus-host disease (GVHD) is the most serious and challenging complication of allogeneic haematopoietic stem-cell transplantation (HSCT). There is a need for developing new approaches to mitigate GVHD and ultimately facilitate the use of allogeneic HSCT for the treatment of haematological cancers. In this Review, the authors discuss rationale, clinical evidence, and outcomes of the current GVHD prophylaxis and assess the clinical evidence for emerging approaches in the prevention of GVHD.

The sinonasal cavities are affected by a range of tumour types, the most common of which are sinonasal squamous-cell carcinoma (SNSCC) and intestinal-type adenocarcinoma (ITAC). Compared with the main types of head and neck cancer, these sinonasal cancers have distinct epidemiological, clinical, aetiological, pathological and genetic characteristics, and require specialized treatment, bearing in mind their important anatomical location. All these aspects of ITAC and SNSCC are reviewed in this article.

Metronomic chemotherapy has undergone major advances as an antiangiogenic therapy. The discovery of the pro-immune properties of chemotherapy has established the intrinsic multitargeted nature of this therapeutic approach. André et al. describe the complex mechanisms of action of metronomic chemotherapy, and discuss the latest clinical data in both adult and paediatric populations, highlighting its potential role in the era of personalized medicine.

Around 20% of patients with colorectal cancer (CRC) have synchronous hepatic metastases at the time of presentation, highlighting the need for appropriate diagnostic and staging assessments. Furthermore, various approaches to the therapeutic management of such patients are available, and the treatment strategy used is influenced by clinical presentation. Herein, these aspects of the management of patients with CRC and synchronous liver metastases are comprehensively reviewed, focusing on the integration of surgical approaches within a multidisciplinary framework.

The combination of conventional anatomical MRI and functional magnet resonance sequences–known as multiparametric MRI (mp-MRI) is emerging as an accurate tool for identifying clinically relevant tumours. This Review discusses the role of mp-MRI in the detection, staging, and treatment planning of prostate cancer.

MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy; however, MEK1/2 inhibitors have been shown to have efficacy in only a narrow range of cancer types, mainly tumours that harbourBRAF or NRASmutations. In this article, the clinical experience with MEK inhibitors to date is reviewed, and potential approaches to overcoming therapeutic resistance and increasing the efficacy of treatment are discussed.

High-risk prostate cancer includes a heterogeneous group of patients with a range of prognoses, with some that can be fatal. The optimal management of this patient subgroup is evolving. We critically evaluate the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care.

Over 70 years ago, Huggins and Hodges discovered that prostate cancer depends on androgens. Since then, targeting the androgen receptor signaling pathway has remained the backbone of prostate cancer treatment. This Review discusses the past, present and future of androgen receptor targeting therapeutics.

Men who are elderly constitute a unique patient group who are often denied effective treatments for fear of toxicity or diminished efficacy or are unduly subjected to intense therapies despite multiple comorbidities and indolent disease. This Review highlights the importance of individualizing therapy based on the comorbidities, functional status, nutritional status and aggressiveness of disease rather than age alone.

Low-risk prostate cancer is diagnosed in nearly half of men undergoing screening. About a third of these men harbour high-grade cancer that is not detected by conventional systematic biopsy. Should we treat men with low-risk prostate on the basis that it might be of higher grade than it seems? Should we treat it to prevent future progression to a more aggressive form of cancer? What are the nonivasive treatment options for these men? In this Review, Mark Emberton and Laurence Klotz discuss the two current choices to manage low-risk prostate cancer: active surveillance and focal therapy.

Metastatic prostate cancer and its treatment are associated with skeletal complications, which cause some of the most distressing symptoms as well as being associated with poor survival. This Review addresses the therapeutic options that exist to treat the morbidity associated with skeletal-related events.

Circulating tumour cells (CTCs) might be representative of the tumour burden and might also provide information on tumour cell biology. As such, these cells hold promise in the prediction and monitoring of response to anticancer therapy. In this Review, the authors highlight the challenges of monitoring treatment response in metastatic castrate-resistance prostate cancer and discuss the developments in CTC analyses that have increased the value of these cells as potential biomarkers in this disease.

Chemotherapeutic agents targeting thymidylate biosynthesis, and particularly the enzyme thymidylate synthase, have now been key cancer therapies for 60 years. In this article, the classic and novel approaches to targeting this metabolic pathway and strategies for overcoming drug resistance mechanisms are comprehensively reviewed.

Identification of the optimal dose remains a key challenge in drug development. The standard approach that is based on identifying the maximum tolerated dose does not take into account important aspects of clinical pharmacology for newer targeted agents. The authors discuss adaptations to dose-finding trials for molecularly-targeted agents that enable more-efficient trials in the future in terms of costs and, most importantly, optimal patient benefit.

Soft-tissue sarcomas (STS) are a rare and heterogeneous group of tumours, with a wide range of differing behaviours and underlying molecular pathologies. Recent advances in molecular pathogenesis, novel targeted therapies, changes in clinical trial design and increased international collaboration have led to the development of histology-driven therapy. The authors of this Review describe the current gold standard treatment for specific STS subtypes and outline the future promising therapies in the pipeline.

Individuals with Li-Fraumeni syndrome, who carry germline mutations in theTP53 gene that encodes the tumour-suppressor protein p53, are at high risk of developing cancers in multiple organs. In this Review, considerations for cancer screening and management in carriers of TP53mutations are discussed, and an evidence-based approach to cancer surveillance in such individuals is proposed.

Patients infected with HIV seem to develop certain types of cancer more frequently than uninfected people. Specifically, lymphomas represent the most frequent malignancy affecting patients with HIV. This Review focuses on the different type of lymphomas that generally occur in patients infected with HIV, as well as other cancers. The authors provide an update of epidemiological data and diagnostic issues, and discuss the most-appropriate strategies for the management of patients with both HIV and lymphomas.

In September 2012, over 100 experts in cancer research in Africa met in London to discuss the challenges in carrying out high-quality research in this continent. This Review summarizes the discussions and recommendations of this meeting and many examples of successful programmes that have enhanced the development of research in Africa. It also discusses the next steps required to create programmes that will enable evidenced-based cancer control approaches.

Brain metastasis is an important complication associated with a number of common primary cancers, including lung and breast cancers, and melanoma, and has major effects on patient morbidity and mortality. This Review discusses the advances in our understanding of the molecular biology of brain metastases, and how this knowledge has influenced the imaging, surgical, radiological and pharmaceutical approaches involved in the management of brain metastasis.