Review Articles in 2013

Evidence indicates that reductions in recommended doses of chemotherapy often occur among obese patients with cancer. ASCO guidelines recommend that chemotherapy dosing in obese patients should be calculated based on actual weight, rather than the current practice based on estimation of body surface area. In this Review, chemotherapy dosing in this population is discussed along with how future research could lead to a more-personalized approach.

As heterogeneity increasingly needs to be taken into account in the treatment of solid tumours, methods to detect genetic variation have come to the fore. One method that might have considerable clinical utility is the detection of variations in circulating-free DNA. This Review outlines the possibilities and challenges that this technique offers in terms of predictive and prognostic markers, as well as in the detection of therapy resistance.

Insights into tumour biology require biospecimens from the primary tumour and those that reflect the patient's disease in specific contexts. Tumour samples must be representative, viable, and adequate both in quantity and quality for subsequent molecular applications. This Review article outlines the existing procedures for sample procurement and processing of next-generation biospecimens, and highlights the issues involved in this endeavour.

Definition of complete remission in patients with acute myeloid leukaemia (AML) represents a highly heterogeneous state associated with diverse clinical outcomes. The use of minimal residual disease (MRD) as a response criterion allows efficacy assessment of AML therapy. The authors review the characteristics and challenges of the modalities used to detect MRD and outline opportunities to improve clinical use of MRD measurements.

Highly efficacious vaccines are available to protect against persistent human papillomavirus (HPV) infection and, therefore, the associated neoplasias (most notably cervical cancer). This Review article discusses the two approved vaccines in terms of their structure, mode of action, efficacy, cross-reactivity with non-vaccine HPV types, safety and use in vaccination programmes.

Although patients with melanoma generally benefit from BRAF or MEK targeted therapies, adverse events can occur on treatment, including the emergence of second malignancies. Evidence suggests unintended or paradoxical activation of MAPK signalling might underlie the majority of these second malignancies. The authors discuss the basis for this paradoxical MAPK activation, and the rationale for novel therapeutic strategies for the management of BRAF-inhibitor-induced neoplasia.

Circulating blood biomarkers are promising non-invasive real-time surrogates for tumour tissue-based biomarkers, and in breast cancer they have been used as tools for diagnosis, prognostication, prediction, monitoring of therapeutic response, and resistance. This Review outlines the techniques, challenges and possibilities of this promising area.

Charged particle therapy (CPT) offers advantages over conventional radiotherapy, such as higher local control of the tumour and the potential for less damage to healthy tissues. Despite the advantages of CPT, only a small number of controlled randomized clinical trials have compared it to conventional radiotherapy. The latest clinical data on the use of CPT, dose calculations and delivery, cost-effectiveness issues, current status, and future directions are discussed.

Lung cancer is the leading cause of cancer death in the world. Although smoking cessation will have the greatest impact on lung cancer development, chemoprevention could prove to be very effective. The authors discuss the principles of chemoprevention, including data from preclinical models, completed clinical trials and observational studies, and describe new treatments for novel targeted pathways and future chemopreventive efforts.

In selected patients with early stage breast cancer, accelerated partial breast irradiation (APBI) has emerged as an alternative treatment option to whole breast irradiation. The authors of this article review the available modalities, patient selection criteria and consensus guideline recommendations, and current controversies in APBI, and discuss why it has become an accepted therapy for suitably selected patients outside of clinical trials.

Although surgery is a requirement for a potential cure from pancreatic cancer, it is usually diagnosed at a late stage, when surgical intervention is not straightforward. This Review article outlines the controversies surrounding the treatment options for patients with advanced-stage pancreatic cancer, from surgery through to chemotherapy, radiotherapy, targeted agents and palliative care.

For patients in low and middle-income countries (LMICs), many of the advances in medical oncology enjoyed in the developed world are nothing but an aspiration for the future. However, as Gilberto Lopes Jr and colleagues describe, LMICS are using generic and biosimilar drugs, expanding participation in clinical trials, implementing universal health-care schemes, using compulsory licensing schemes and increasing public–private partnerships to increase access to cancer medications for their citizens.

Describing data from preclinical studies and early clinical trial results, Azad et al. suggest that low-dose epigenetic-modulating agents can reprogramme tumour cells and override any immediate cytotoxic effects that are typically observed at high doses. Such optimization of drug dosing and scheduling of currently available epigenetic therapies could give these agents a prominent place in cancer management—when used alone or in combination with other therapies.

T cells can be genetically modified to express chimeric antigen receptors (CARs) that target CD19, which is expressed by B cell malignancies, but not by normal tissues. This Review outlines the use of CARs in the treatment of these malignancies and states that it is likely to become an important therapy option for these patients.

The occurrence of second malignant neoplasms in survivors of cancer is one of the most serious complications of cancer and its treatment. Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. This Review article discusses the wide-range of factors that influence the occurrence of second malignant neoplasms and a review of modifiable behavioural and lifestyle factors.

With increasing numbers of anticancer drugs requiring testing, new adaptive model-based phase I trial designs can improve on current practice by exploring a wider range of dose combinations than standard phase I methods. In this Review, the authors describe the methods available as well as the opportunities and challenges faced in dual-agent phase I trials.

There have been great advances in the treatment of patients with breast cancer, with novel targeted agents having a great impact on treatment at all stages of the disease trajectory. In this Review, the treatment options for patients with metastatic disease are discussed—focussing on agents that target breast cancer cells, breast cancer stem cells and the breast microenvironment.

To improve treatments for patients with castration-resistant prostate cancer, new biomarkers and surrogate end points for clinical trials are required. Identifying biomarkers that reflect clinical benefit and that guide personalized treatment plans are of the highest priority. This Review article outlines the framework for developing such biomarkers, including analytical validation, clinical validation and regulatory approval, and describes promising emerging biomarkers.

Advances in surgical oncology have improved patient safety and provided less-invasive procedures. In the era of personalized medicine, the value of surgical specimens for understanding tumour biology, extended indication of surgery, the role of surgical oncology in trials that examine neoadjuvant therapy in patients selected by appropriate biomarkers, and the possibilities to personalize the surgical procedure itself according to lung cancer subtypes are discussed.

Agents targeting the PI3K/AKT/mTOR pathway have been shown to be safe and effective in treating a number of tumour types. This Review outlines the background to these inhibitors and discusses the second-generation inhibitors of this pathway. The authors propose that the way forward for the development of inhibitors of the PI3K/AKT/mTOR pathway might be a systems biology approach and biomarker-driven studies.