Review Articles in 2017

Patients with c-MET-expressing colorectal or gastrointestinal cancers generally have worse outcomes than those of patients whose tumours have low levels of, or absent c-MET expression. However, c-MET targeted agents have, thus far, failed to show clinical efficacy. In this Review, the authors describe the opportunities and challenges created by the clinical implementation of c-MET targeted therapies.

In less than a decade, the treatment landscape of metastatic melanoma has changed dramatically. Novel targeted agents and immunotherapies are revolutionizing patient outcomes, but the range of available drugs complicates clinical decision-making. Herein, the authors chart the therapeutic advances and review the current evidence that can be used to guide therapeutic decisions for individual patients with metastatic melanoma, highlighting knowledge gaps.

Conventional radiotherapy with X-rays is being replaced by radiotherapy with high-energy charged particles, an approach that better spares healthy tissue from radiation but is associated with higher costs. Evidence supporting the cost-effectiveness of either modality can only come from the results of randomized clinical trials. The authors of this Review discuss ongoing randomized trials of charged-particle therapies as well as aspects related to radiobiology, which need to be taken into account in order to fully exploit the therapeutic potential of charged particles.

Analysis of circulating tumour components using liquid biopsy approaches holds considerable promise to improve the detection and treatment of cancer. In this Review, Alberto Bardelli and colleagues outline how different forms of liquid biopsy, and particularly the assessment of circulating tumour DNA, can be exploited to guide patient care, and discuss the progress made to date in integrating such analyses into the clinic.

Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.

By preventing the accumulation of misfolded or damaged proteins, the ubiquitin-proteasome pathway has essential functions in cell homeostasis. Cancer cells produce proteins that promote cell survival and proliferation, and inhibit cell death, and thus, clinical trials have tested the therapeutic effect of proteasome inhibitors on patients with a variety of cancer types, mainly haematological malignancies. Herein, the authors discuss the advances and challenges derived from the introduction of proteasome inhibitors in the clinic, including therapeutic resistance.

The interaction between radiotherapy and the host immune system has uncovered new mechanisms that can be exploited to improve the efficacy of radiotherapy. In this article, the authors highlight data providing new explanations for the success or failure of radiotherapy, and postulate, using radiation-induced tumour equilibrium (RITE) as an example, how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure.

Intraoperative fluorescence enables highly specific real-time detection of tumours at the time of surgery. In particular, near-infrared (NIR) fluorescence is a promising tool currently being tested in clinical settings. Zhang et al. discuss the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, as well as the challenges associated with their effective application in clinical settings.