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A study assessing the impact of the 21-gene recurrence score assay in routine clinical practice on the use of adjuvant chemotherapy in women with early stage ER-positive breast cancers showed that adjuvant chemotherapy use decreased in high-risk patients, but increased in low-risk patients. I discuss these results and highlight how this reflects more-selective administration of chemotherapy.

In the RADIANT study, no difference in disease-free survival was observed for patients with non-small-cell lung cancer (NSCLC) treated with erlotinib versus placebo in the adjuvant setting. Further biomarker studies are awaited to determine whether patients with NSCLC can benefit from adjuvant therapy with tyrosine kinase inhibitors.

In two recent phase III trials, investigators evaluated the addition of docetaxel to androgen-deprivation therapy for non-castrate prostate cancer. On the basis of the CHAARTED-trial findings, we can firmly conclude that this combination can be used in the metastatic setting. The results of the GETUG 12 trial are less informative, although some benefit for patients with high-risk localized prostate cancer was demonstrated.

The improved understanding of the molecular mechanisms that drive tumorigenesis has led to the development of molecularly targeted agents (MTAs) that inhibit specific proteins or pathways. However, the rate of drug approvals remains disappointingly low in oncology. The authors of this Review discuss several aspects of phase I trials that are evolving in the MTA era in order to adapt to the changing nature of cancer therapies and to expedite their clinical translation.

Several novel strategies have harnessed the ability of T cells to target cancer cells. Each treatment approach is based on unique platforms that should encourage development of further therapeutic agents in the future. The authors describe the background and development of distinct immunotherapy platforms, summarize the scientific advances in understanding the mechanism of action of each therapy, and discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.

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.

Genetic testing for cancer susceptibility remains focused on specific individuals identified based on their personal and family history of the disease. Wider population-based screening has been applied to specific groups with a known high prevalence of high-risk mutations in cancer-related genes. This Review describes the studies that support the feasibility and cost-effectiveness of this approach, with particular regard to testing for founderBRCA1/2mutations in Ashkenazi Jewish populations. These studies, together with the falling costs and increasing availability of genetic assays, advances in preventive medicine, and growing demand from individuals for their genetic information, have broadened interest in genetic testing for cancer susceptibility in increasingly large demographic groups; thus, the opportunities and challenges of the different potential population-based approaches that are predicated on specific genes, gene panels, the entire exome, or the whole genome are also discussed herein.

The molecularly targeted therapy paradigm has led to improvements in the management of patients with cancer. Responses to targeted therapies are, however, mostly short-lived, owing to inherent or acquired resistance, which in most cases relates to the outgrowth of pre-existent rare subclones harbouring resistance mutations. Our current understanding of this concept is reviewed herein; how knowledge of pre-existing resistance mechanism obtained through the use of ultra-sensitive sensitive DNA-sequencing assays might be best exploited to improve personalized medicine is discussed.

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.

The incidence of cancer in transplant recipients is indisputably higher than that of the age-matched general population, and the increased cancer development in transplant recipients who require immunosuppression to avoid graft rejection is well recognized. This Review discusses the advances with mTOR inhibitors that interfere with tumour development via immune and non-immune mechanisms, and the current and future perspectives on how best to normalize the unacceptably high rates of post-transplantation malignancies are highlighted.