Review Articles in 2015

Metronomic chemotherapy has shown promising efficacy and minimal toxicity in patients with advanced-stage breast cancer. Moreover, the low cost of this regimen represents an opportunity for its expanded utilization, especially in developing countries. In this Review, the authors discuss the key clinical advances, including new trial design, appropriate patient and end point selection, and the evolving rationale for metronomic chemotherapy combinations.

Many breast cancer survivors experience long-term adverse effects of adjuvant systemic therapy, including cognitive decline. The decline of cognitive functions can have a detrimental impact on quality of life and might interfere with independent living. This Review discusses the tissue-selective side effects of endocrine therapies and specifically their impact on cognitive function. The critical issues that need to be addressed to best assess the cognitive effects of endocrine treatment in patients with breast cancer are highlighted.

The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The authors discuss the limitations, including the identification of driver events, and the possible solutions to the application of precision medicine in the management of patients with metastatic disease, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.

The use of traditional Euclidean geometry can present challenges for analysis of image characteristics, particular those of extremely complex biological structures, obtained by medical and scientific imaging modalities. Fractal geometry is a potentially complementary mathematical approach that enables efficient estimation of geometrical complexity, and the irregularity of shapes and patterns. This Review introduces the concept of fractals and fractal geometry, and describes how analysis of fractal (non-integer) dimension and associated measurements, such as lacunarity (texture), can be performed and applied to the analysis of cancer. The authors discuss how fractal analysis might provide information on many diverse biological structures relevant to the natural history of lung cancer, which might prove useful for the diagnosis and management of this disease.

Tumour-promoting inflammation is an enabling characteristic of many cancers. Conversely, many cancers can cause inflammation. Inflammation in the tumour microenvironment arises from the interplay of many different inflammatory cells and mediators, many of which are potential treatment targets. Herein, the authors review our current knowledge of the interplay between inflammation and tumorigenesis and discuss the potential of treatments that target cancer-related inflammation.

Endocrine resistance will eventually develop in patients with ER-positive breast cancer receiving endocrine therapy. Several studies unveiled gain-of-function mutations in theESR1 gene in approximately 20% of patients with metastatic ER-positive disease who received endocrine therapies. These mutations lead to ligand-independent ER activity that promotes tumour growth, partial resistance to endocrine therapy, and potentially enhanced metastatic capacity. We discuss the contribution of ESR1mutations to the development of acquired endocrine resistance, and evaluate how mutated ER can be detected and targeted to overcome resistance and improve patient outcomes.

Although dramatic changes in the delivery of radiation therapy have occurred, the impact of radiobiology on the clinic has been far less substantial. New advances are uncovering some of the mechanistic processes that underlie the differences between the tumour and host tissue characteristics. The authors of this Review focus on how these processes might be targeted to improve the outcome of radiotherapy for patients.

Liver cancer mortality has increased in the past 20 years, and estimates indicate that the global health burden of this disease will continue to grow. Advances in our knowledge of the human genome have provided a comprehensive picture of commonly mutated genes in patients with hepatocellular carcinoma (HCC). In this Review, the authors summarize the molecular concepts of progression of HCC, discuss the potential reasons for clinical trial failure, and propose new concepts of drug development.

Adolescent or young adult (AYA) patients with cancer are a unique group, with unique clinical needs; these patients are not entirely suited to cancer treatment and managment strategies designed either for paediatric patients, or older adult patients. In this Review, issues associated with the treatment, management and long-term outcomes of AYA patients with cancer are described in the context of acute lymphoblastic leukaemia and melanoma.

Hormone-receptor-positive breast cancer accounts for the majority of all breast cancers. The evolution of this disease from early stage to the metastatic setting leads to increased heterogeneity and the development of treatment resistance representing a great challenge for management decisions. In this Review, we examine the current evidence that can guide treatment decisions in patients with advanced-stage ER+ breast cancer, discuss how to tackle these therapeutic challenges and provide suggestions for the optimal management of this patient population.

Transarterial therapies in the setting of primary and secondary liver malignancies are an essential part of the oncology landscape. Most patients are not amenable to curative surgical intervention, which necessitates the use of alternative treatments that preserve quality of life whilst providing clinical benefit. The authors of this Review discuss intra-arterial techniques in light of the current levels of evidence to support their appropriate use in various clinical settings.

The recognition of non-small-cell lung cancer (NSCLC) as a heterogeneous disease and ongoing efforts to characterize disease subtypes based on genotype and histology have resulted in dramatic improvements in outcomes for select patient subgroups. However, many challenges remain, not least acquired therapeutic resistance and the related issue of how to best use the available therapies. In this Review, the authors provide an overview of the key developments in NSCLC therapy, describe efforts to tackle therapeutic resistance, and discuss potential strategies to further optimize patient outcomes by stratifying treatments according to particular disease subtypes.

PET has evolved from a purely diagnostic imaging technique to a multifunctional modality that can provide diverse information of relevance to oncological management. This modality might offer the potential to improve patient care and outcomes by enabling better disease characterization, treatment-response monitoring, and follow-up assessment. Herein, the authors discuss the data supporting the use of PET in personalizing the clinical management of patients with locally advanced and metastatic non-small-cell lung cancer.

Traditionally, intertumour heterogeneity in breast cancer has been documented in terms of different histological subtypes, treatment sensitivity profiles, and clinical outcomes among different patients. High-throughput molecular profiling studies have confirmed that spatial and temporal intratumour heterogeneity of breast cancers exist at a level beyond common expectations. In this Review, the authors describe the different levels of tumour heterogeneity, and discuss the strategies that can be adopted by clinicians to tackle treatment response and resistance issues associated with such heterogeneity for the optimal clinical management of breast malignancies.

Cancer stem cell (CSC) populations are increasingly recognized in most malignancies and are hypothesized to contribute to cancer proliferation, relapse, and metastasis. Thus, the highly conserved stem-cell signal transduction pathways involved in development and tissue homeostasis that are frequently active in CSCs represent prime targets for targeted therapies against this characteristically treatment-resistant and highly tumorigenic cell population. This Review provides a update on the clinical development of therapies targeting Wnt, Notch, and Hedgehog, three prominent stem-cell signalling pathways that are upregulated in CSCs.

Although neoadjuvant chemotherapy (NACT) does not prolong survival compared with adjuvant chemotherapy, this approach does not increase the risk of locoregional recurrence, and the high rates of response following NACT have had a considerable impact on locoregional treatment considerations. In particular, NACT can decrease the need for mastectomy and axillary lymph-node dissection. This Review discusses issues relating to the identification of ideal candidates for NACT, and also those surrounding surgery of the breast and axilla in women with breast cancer who receive NACT.

The survival rates of patients with pancreatic cancer are low and have not improved significantly over the past three or four decades. Thus, effective treatments for this disease are an urgent unmet need. Novel treatment paradigms will probably be required, and many new therapeutic approaches are being tested in this setting. This Review outlines the state-of-the-art therapies for patients with pancreatic cancer, as well as the novel treatment strategies that are the focus of drug-development efforts.

The development and implementation of more effective genome analysis technologies has enabled substantial improvements in our understanding of the genomic changes that take place in patients with acute lymphoblastic leukaemia (ALL). This Review provides a detailed summary of advances in our understanding of the genomics of ALL, and describes how these advances might lead to improved patient outcomes.

Patient-reported outcome (PRO) measures, such as quality of life, have been associated with relevant clinical end points and are prognostic for survival outcomes in a variety of solid cancers in adults. The authors of this Review comprehensively assess the correlation of PROs with treatment response and survival, and explore tumour-related and patient-centric composite end points in patients with cancer participating in clinical trials.

The evolutionary biology of cancers and organismal species are similar: in both cases, a genetically diverse population mutates and evolves through natural selection. In addition, driving both species and cancers to extinction is extremely difficult. Nevertheless, greater than 99.9% of species that have lived on Earth are now extinct, and the parallels between tumours and organismal evolution suggest that understanding species extinction through paleontology could teach us much about how to eradicate cancers. In this Review, the selective pressures that have driven species extinct and the characteristics of species that make them resistant to extinction are described, and how these factors can be translated to cancers in order to develop improved approaches to therapy and prognosis is discussed.