Perspectives in 2018

Precision medicine approaches to the treatment of cancer are largely reliant on genomic analysis alone. In this Perspective the authors provide a rationale for the incorporation of analysis of the proteome, which is a rich source of biological heterogeneity, into the treatment and management of patients with cancer.

Integrating molecular nuclear imaging in clinical research has great potential to improve anticancer therapy, particularly through the development of imaging biomarkers. Herein, the multistage process of developing novel molecular imaging biomarkers is discussed, highlighting both the challenges that have restricted the use of molecular imaging in clinical oncology research and future opportunities in this area.

Many clinical trials are testing the safety and/or efficacy of combining radiotherapy with immunotherapy, nearly all using a single-site irradiation (or ‘abscopal’) approach, but emerging evidence suggests that this approach likely produces suboptimal results. The authors of this Perspective provide a biological rationale supporting the abandonment of the abscopal approach, and instead advocate exploring comprehensive irradiation of multiple/all lesions.

With the expansion of the precision medicine paradigm, seamless trial approaches to drug development hold great promise for accelerating the accessibility of novel therapeutic agents but are also accompanied by important trade-offs. The authors describe several opportunities to improve the efficiency of drug development in oncology, as well as new mechanisms to obtain information about anticancer therapies throughout their life cycle.

Liquid biopsy approaches hold great promise in early cancer diagnosis or minimal residual disease monitoring for cancer recurrence. Herein, the authors evaluate contemporary next-generation sequencing approaches to circulating tumour DNA detection in these contexts, with a focus on studies in patients with non-small-cell lung cancer. They discuss the feasibility of introducing these strategies into the clinic, highlighting the technical and analytical challenges, as well as possible solutions.

Despite extensive research efforts, very few DNA methylation-based biomarkers have been implemented clinically. In this Perspective, the authors describe the importance of considering the genomic locations examined in determining the diagnostic or prognostic relevance of putative DNA methylation-based biomarkers.

Emerging evidence indicates that the composition of the intestinal microbiota influences anticancer immunosurveillance and therefore the effectiveness of anticancer therapies, especially immune-checkpoint inhibitors. Herein, key contributors to this field of research discuss these connections between gut bacteria, anticancer immunity, and general health, with a focus on specific bacterial species consistently associated with favourable clinical outcomes of anticancer immunotherapy, and explore the potential mechanisms.