Review Articles in 2012

Breast cancers in young women are typically aggressive and so young age can correlate with a poorer outcome. In this Review article, Steven Narod discusses the risk factors, risks of recurrence and secondary cancer, treatment, prevention and awareness of very-early onset breast cancer.

Hodgkin lymphoma has become one of the most successfully treatable cancers; nevertheless, adverse treatment-related side effects still occur. In this Review, Borchmann et al. discuss the current choices for patients with Hodgkin lymphoma by finding the balance between optimal disease control and the risk of long-term sequelae.

Gliomas in children differ from their adult counterparts by histological grade, site of presentation and rate of malignant transformation. Molecular profiling experiments on adult high-grade glioma have revealed key biological differences between the adult and paediatric disease. The authors summarize the current and historical data, compare and contrast the findings in these tumours across age groups, and discuss the implications for paediatric patients whose treatment options are modelled on clinical data from adult patients.

Cancer and its associated treatment cause debilitating symptom clusters including sickness, nausea, fatigue, pain, distractibility and poor memory. The authors of this Review describe what is known about the mechanisms of the behavioural comorbidities experienced by cancer patients, discuss how cancer-related symptoms develop, and what can be done at the clinical and preclinical levels to better understand their mechanisms and identify appropriate treatments.

Neuroblastoma is a debilitating disease and a leading cause of childhood cancer deaths. The discovery of ALK as a mutated oncogenic receptor in neuroblastoma has provided an attractive target for innovative therapies. In this article, Mosse and Carpenter review the preclinical and clinical advances in ALK-targeted therapies for neuroblastoma and discuss the emerging challenges.

Targeting the MET pathway is an increasingly attractive anticancer strategy. In this Review, this pathway is viewed from the clinical perspective, assessing the available agents in terms of efficacy and toxicity and looking forward to biomarker-driven application in the clinic.

Cancer cells rely on angiogenesis to fulfil their need for oxygen and nutrients; hence, agents targeting angiogenic pathways and mediators have been investigated as potential cancer drugs. However, a significant number of patients either do not respond to antiangiogenic agents or fairly rapidly develop resistance to them, which raises questions about how resistance develops and how it can be overcome. In this Review, the authors examine the evidence linking antiangiogenic agents and intratumour hypoxia by providing an overview of the preclinical and clinical data, focusing on the possibility of exploiting intratumour hypoxia as a means to improve the therapeutic response to antiangiogenic agents.

Tyrosine kinase inhibitors, such as imatinib, are effective treatments of advanced-stage gastrointestinal stromal tumour. Here, the optimal treatment strategy for these patients is outlined and future challenges discussed.

In this Review, Tentler et al. present the opportunities and challenges of using patient-derived tumour xenograft models in oncology drug development, provide specific disease examples, and describe concepts regarding predictive biomarker development and future applications.

The advances in the field of targeted therapy for the treatment of renal cell carcinoma have improved outcomes for patients dramatically. In this Review article, an expert consensus opinion for the optimal use of these targeted anticancer therapies for the treatment of patients with renal cell carcinoma is outlined.

Crizotinib has provided dramatic and prolonged benefit for patients with the ALK-positive subtype of non-small-cell lung cancer. Despite these early successes, many challenges remain including understanding the mechanisms of resistance to crizotinib. This Review examines what we already know and the major emerging questions associated with optimal management of this disease.

The authors of this Review discuss the mechanism of action of aspirin, current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin.

Screening to detect preneoplastic lesions has the potential to substantially reduce oesophageal cancer mortality and morbidity. In this Review, the authors discuss the advantages and disadvantages of different screening methods, the psychological and economic implications of oesophageal cancer screening, and the feasibility of implementing a screening programme for the disease.

We know exercising keeps us healthy; what is less self-evident is whether patients undergoing active treatment or following the completion of therapy for cancer may also benefit from exercise rehabilitation. This Review outlines the effects, mechanisms and clinical importance of anticancer treatment on cardiorespiratory fitness, as well as the efficacy of supervised exercise training to mitigate and/or prevent the adverse impact of a cancer diagnosis on fitness.

Is there a precise end point that could enable us to compare neoadjuvant and adjuvant endocrine therapy outcomes? A reliable short-term surrogate to assess the potential of endocrine drugs in the adjuvant setting? In this Review, Goncalves et al. summarize the studies in which the proliferation marker Ki 67, measured during neoadjuvant treatment, has predicted accurately and consistently the results of much larger studies in the adjuvant setting.

The current system for the development of anticancer drugs is not fit for purpose. In this Review article, this system is examined from the perspective of the drug company, offering a fresh look at development from target identification up to registration.

Despite advances in treating multiple myeloma with the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, most patients eventually relapse. In this Review, the authors discuss how next-generation inhibitors and immunotherapy agents have been developed based on an improved understanding of the biology of the disease, and highlight the challenges associated with these therapeutic approaches.

DNA repair as a therapeutic target has received considerable attention in the treatment of non-small-cell lung cancer (NSCLC). In this Review, Postel-Vinay et al. discuss how optimizing treatment of NSCLC according to DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, may aid clinical decision making and improve the outcome of patients with NSCLC.

Should dynamic contrast-enhanced (DCE)-MRI be used in the assessment of drug-development of antivascular agents? In this Review, O'connor et al. discuss whether data from DCE-MRI are reliable and reproducible biomarkers of drug efficacy, and whether they assist in dose selection and drug scheduling in the design of early clinical trials.

Patients with cancer who also have hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have a significant morbidity and mortality. HBV reactivation is a serious but preventable complication of immunosuppressive therapy. The authors discuss the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with the reactivation of HBV and HCV during immunosuppressive therapy, and discuss strategies for the prevention and treatment of viral reactivation.