Volume 13 Issue 6, June 2016

The rapidly rising costs of cancer care, driven in particular by the high prices of new drugs, are increasingly challenging health-care systems across the world. To ensure accessibility to novel antitumour drugs, novel paradigms are needed at several levels, not only economically, but also in terms of research and new study designs.

Escalating costs of cancer treatments are threatening access to high-quality care. This economic trend comes at a time of unprecedented opportunity for translational research, but an alarmingly low level of patient participation in clinical trials. Patients' concerns about costs are a barrier to trial enrolment, and addressing these concerns is a moral and practical imperative if we are to accelerate progress against cancer.

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.

The characterization of gastroesophageal cancer into subtypes on the basis of diverse genotypes has evolved; however, patients require new treatment options, particularly when standard therapies are exhausted. Improved molecular classification of gastroesophageal cancer subtypes enhances patient selection for biological therapy. The authors of this Review summarize the current awareness of the unique biology of gastroesophageal cancer and discuss the clinically applicability of these findings.

Mucinous colorectal cancer has, in the past, been associated with inferior responses to treatment, and worse patient outcomes compared with other colorectal cancer subtypes; although, this situation has improved in the past 10–15 years. In this Review, the authors describe the key developments that have enabled these improvements, in addition to the potential for further improvements in the care of patients with mucinous colorectal cancer.

Clinical trials of CAR-T-cell therapy for patients with B-cell malignancies have yielded impressive results. Ongoing clinical trials are now testing CAR-T-cell therapies with new designs for the treatment of other haematological and solid malignancies. The authors of this Review present an overview of the approaches that are currently being tested in registered clinical trials, and discuss strategies that can increase the antitumour efficacy and safety of CAR-T-cell therapy.

Patients with advanced cancer often have no access to potentially effective targeted drugs, despite expressing a known biomarker of a marketed drug. However, if the agent is not licensed for that particular malignancy, the only solution is to prescribe the drug off-label or not at all. Tumour molecular profiling can exacerbate this dilemma. The authors of this Perspectives discuss the French AcSé Programme that aims to provide access to molecular testing and the option to receive targeted drugs outside of planned or approved marketing indications in a manner that is safe and further builds on the evidence-base for the use of such agents.