Reviews & Analysis

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.

For cancer therapies to succeed, induction of an anticancer immune response is required. Immuno-oncology approaches are shaping the treatment landscape for patients with advanced-stage melanoma and other solid tumours. These new approaches may enhance immune system activity to improve outcomes, including the potential to achieve long-term survival benefits in many patients.

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.

The recent IBIS-II clinical trial results demonstrate anastrozole reduces breast cancer incidence by 53% in postmenopausal women. While this is a major advance in prevention research, its impact on clinical practice will ultimately depend upon subject perception of risk, adverse effects and benefits of anastrozole versus other available cancer preventive therapies.

Between 2005 and 2007, mutations in JAK2 and MPL were described in most patients with myeloproliferative neoplasms (MPN). These seminal discoveries have forever changed our diagnostic approach to MPN. In December 2013, mutations in CALR were reported in MPN wild-type for JAK2 and MPL. These mutations provide additional diagnostic and prognostic tools in MPN.

Systems biology approaches are beginning to provide information that will enable a more complete view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within the tumour and surrounding microenvironment, both at the organ and organism level. This Review describes the potential of these systems-based approaches and how they are becoming vital for the development and implementation of effective drug discovery and personalized cancer therapy.

Bilateral mastectomy is used to treat an increased percentage of women with unilateral breast cancer in order to prevent a second primary cancer in the unaffected breast. Although this surgical approach has been proposed to benefit women at high risk of contralateral cancer, the decision to remove the contralateral breast is controversial and requires a careful evaluation on an individual basis. This Review discusses the risk factors for contralateral breast cancer, and the evidence that bilateral mastectomy might in fact reduce breast-cancer associated mortality.

The discovery of miRNAs in body fluids has opened up the possibility of using them as non-invasive biomarkers in cancer detection and as predictors of therapy response in cancer treatment. This Review article considers the latest developments in the use of circulating microRNAs as prognostic and predictive biomarkers and discusses their utility in personalized medicine.

In 2013, studies confirmed that HPV infection of target cells predisposes to cervical (pre)cancer. In developed countries, HPV screening revealed superior protection than cytology screening. In India, visual inspection of the cervix after acetic acid application significantly reduced cervical cancer mortality after 12 years. Improved survival for women with advanced disease was observed after adjuvant bevacizumab.

The year 2013 has brought more options for patients with metastatic colorectal cancer (mCRC) with new ways to combine traditional agents, further refinement of predictive molecular for EGFR inhibitors and a new salvage option. Molecular profiling could identify subgroups to further improve treatment selection.

In 2013, the treatment of several NSCLC subtypes was refined. PROFILE-1007 and LUX-Lung 3 confirmed that targeted therapy was superior to chemotherapy, whereas NCIC BR19 and PointBreak failed to show superiority of adjuvant gefitinib and combined maintenance therapy, respectively. These studies reinforced some practices and discouraged others, underscoring the need for new prospective studies.

In this Review, Jeff Shrager and Marty Tenenbaum describe the latest generation of Precision Oncology, and the different ways to keep refining it. In Precision Oncology 3.0, each treatment event provides the chance to learn from it so that such treatment can be applied to other patients with similar characteristics without facing the difficult economic and structural challenges of a clinical trial.

Novel approaches for cancer therapy take advantage of the modulation of the immune system. Immunotherapy is however associated with a number of adverse effects and clinicians will need to become familiar with recognizing and managing them. In this Review the authors describes the toxicity profiles for various anticancer therapies based on immunomodulatory agents.

Advances in single-cell molecular analysis are enhancing our ability to explore the mechanisms of metastasis. In this Review, the authors describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test—and readily amenable to serial sampling—have the potential to inform intratumour heterogeneity and tumour evolution.

In 2013, new insights on the molecular features of cutaneous melanoma provided a paradigm shift in our understanding of the biology of this disease. Exploiting immune checkpoint blockade and the use of BRAF-targeted or MAPK-targeted agents contributed to important progress in the treatment and management of cutaneous melanoma.

2013 saw much progress in breast cancer research. Advances in high-throughput technologies continue to refine our knowledge of the molecular biology of breast cancer, and are beginning to give insight into cancer evolution, drug resistance, and how to deploy precision therapeutics.

Next-generation sequencing analysis and characterization of the microenvironment 'field-effect' that promotes hepatocellular carcinoma (HCC) development has revealed critical players and potential targets for chemoprevention. A biomarker-based drug development strategy is needed to improve future HCC clinical trials and therapies.