Opinion in 2015

Repurposing approved, non-anticancer drugs is an attractive strategy for patients with cancer. To date, successes in oncology drug repurposing have been limited, despite strong evidence supporting the use of many different drugs. A lack of financial incentives for drug developers and limited drug development experience within the non-profit sector are key reasons for this lack of success. The authors discuss these issues and offer solutions to seize this opportunity in the interest of patients and societies, globally.

Conducting high-quality prospective clinical trials in surgical oncology remains a challenge. The authors of this Perspectives examine some of the failures in published surgical oncology trials and discuss why they failed, and provide a critical assessment of the established prospective trial methodology in oncological practice and how these methods might be used more effectively in future evaluation of cancer-surgery practice.

Human papillomavirus (HPV)-screening technologies and HPV vaccination are revolutionizing the management of cancers related to this virus, in particular, cervical neoplasms. At present, however, the effectiveness of these modalities is not optimal, owing to the limited scope of HPV-vaccination and cervical screening programmes. In this Perspectives, an international panel of experts describes for the first time a new campaign, termed 'HPV-FASTER', which aims to broaden the use of HPV vaccination coupled with HPV testing to women aged up to 30 years, and in some settings up to 50 years, with the aim of accelerating the reduction in the incidence of HPV infections and cervical cancer. The authors describe the evidence supporting this approach and details on how it might be implemented, discuss the opportunities—particularly in low-resource settings—and challenges associated with the strategy, and highlight key research gaps that need to be addressed in future studies.

Stage IV gastric cancer is incurable and has a very poor prognosis. Although palliative chemotherapy remains the standard of care, increasing evidence indicates that palliative surgery can provide a prognostic and symptomatic benefit. This Perspectives summarizes the recent evidence underpinning the medical and surgical management of incurable gastric cancer, and provides evidence-based recommendations on treatment strategies and avenues for future research.

Response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC). In the past decade, the development of antiangiogenic and anti-EGFR biologic agents, doublet and triplet chemotherapy regimens, and combinations of these treatment modalities has created not only new first-line treatment options, but also new challenges for the management of this disease. In this Perspectives, these advances and the confusion surrounding their implications are discussed. The authors attempt to address some of the challenges in clinical decision-making and propose an algorithm for personalized allocation of first-line treatments in patients with mCRC.

Predictive biomarkers are invaluable for successful and cost-effective treatment of cancer, however, biomarker discovery is difficult and requires multiple independent studies to identify suitable predictors of efficacy. Clinical trials performed in the USA, Europe or Asia can offer unique opportunities for biomarker discovery and validation. In this Perspectives, the authors describe the current fragmented approach to biomarker discovery and validation, highlighting how collaborative engagement of the academic, regulatory and pharmaceutical communities can help address these issues.

Currently, most novel chemotherapies are initially tested in tumour cell lines and xenografts, which generally fail to reflect the full spectrum of tumour-specific mutations, and might explain the low success rates of experimental treatments. In this Perspectives, the mouse hospital co-clinical trial project is described, which enables treatments to be tested in mouse models that accurately reflect the tumour characteristics of individual patients.

A lack of clinical investigation, which has arguably become more pronounced in the past decade, currently hinders progress in cancer surgery research, and ultimately the treatment of patients with cancer. This Perspectives describes the major barriers to progress in surgical oncology, and how improvements might be made in this important, but often overlooked, aspect of cancer treatment.

Several guidelines propose the use of Ki67 expression to select which patients with early stage breast cancer and 1–3 positive nodes should not receive adjuvant chemotherapy. In this Perspective, the authors discuss why, in 2015, the oncologist should not rely on the use of this biomarker for decision-making in this patient population—owing to lack of analytical validity of Ki67 staining, its poor performance for prognostic purposes, and no strong evidence indicating that Ki67 staining predicts the efficacy of adjuvant chemotherapy.

Since February 2012, the FDA has identified widespread infiltration of counterfeit bevacizumab into the US drug-supply chain. This Perspectives uses this case study to highlight the continued lack of information, knowledge, and solutions necessary to protect patients against future breaches in the drug-supply network, as well as the need for collaborative efforts to enhanced surveillance for counterfeit medicines and improve communication of risk information.

The standard treatment for advanced-stage ovarian cancer is upfront cytoreductive surgery, and the extent of residual disease after surgery correlates with response to adjuvant therapy and disease outcomes. This Perspectives article provides an overview of the historical progression of primary cytoreduction and definitions of 'optimal' residual disease. In addition, approaches to personalizing surgical therapy and improving the quality of surgical care are discussed.