Review Articles in 2018

Evidence of the functional roles of non-coding RNAs in cancer is expanding, and the potential of these RNAs as diagnostic and prognostic biomarkers is increasingly recognized. Herein, the authors review the recent developments in these areas and provide compendiums of circulating microRNAs and long non-coding RNAs that have promise as diagnostic and prognostic cancer biomarkers.

In recent years, a number of novel agents have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). Herein, Jan A. Burger and Susan O’Brien outline the emerging paradigm of individualized therapy for patients with CLL aimed at exploiting the advantages of these novel agents but also integrating traditional therapies for selected patients.

Patients with advanced-stage urothelial carcinoma typically receive chemotherapy and might also receive immune-checkpoint inhibitors following disease progression. However, the majority of patients will ultimately develop resistance to treatment. In this Review, the authors describe the evolutionary mechanisms of treatment resistance in patients with urothelial carcinoma.

The multiple myelomas (MMs) are heterogeneous malignancies that are nearly always associated with chromosomal abnormalities, which can be considered either primary or secondary abnormalities. The classification of MM according to the underlying primary cytogenetic abnormality might enable the development of better treatment strategies. The authors describe treatment approaches that consider the current standard of care for patients with MM along with recommendations for certain subgroups of patients.

Patients with sarcomas have historically been treated with surgery and/or chemotherapy, although the outcomes achieved with these approaches, especially in advanced-stage disease, are often disappointing. In this Review, the authors describe the opportunities created by selective use of targeted therapies on the basis of the biological characteristics of individual tumours.

The tumour stroma is a component of the tumour microenvironment and has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote resistance to such therapies. Herein, the authors provide an overview of the complex cancer cell–tumour stroma interactions and discuss how novel treatment strategies should combine anticancer and antistromal agents.

Glioblastoma is a disease associated with a dismal patient prognosis, necessitating the development of novel therapies. Substantial research effort is being devoted to the development of immunotherapies for glioblastoma. Herein, the rationale and promise for this approach are discussed, together with the challenges and how they might be overcome.

Developments in genomic sequencing technologies have enabled increasing amounts of information on the genomes of individual cancers to be revealed. At the same time, increasing numbers of therapies targeting specific genomic alterations are being made available, necessitating the use of genomics to diagnose and treat patients with cancer. In this Review, the authors describe the emerging clinical relevance of genomics in oncology, in addition to the many challenges that currently preclude routine clinical use.

The PI3K–AKT–mTOR pathway has key roles in tumorigenesis and is dysregulated in most cancers. Consequently, numerous drugs that target key nodes of this pathway have been developed, although few of these agents have been approved for the treatment of cancer. Herein, the authors review the current experience with anticancer therapies that target the PI3K–AKT–mTOR pathway, discuss the challenges that have limited the clinical translation of these agents, and provide perspectives for the future development of these drugs.

The development of cancer involves several epigenomic alterations, and the presence of certain alterations before the development of cancer is associated with cancer risk. In this Review, the authors describe the potential of epigenomics-based assays to predict an individual's risk of cancer, including discussions of technical, practical and societal issues regarding the implementation of such assays.

The combination of immunotherapies with other therapeutic modalities, including anti-angiogenic agents, is currently under investigation to improve the outcomes of patients receiving immunotherapies. In this article, the authors review the effects mediated by anti-angiogenic agents that might increase the efficacy of immunotherapies and discuss the possibility that immunotherapies might increase the efficacy of anti-angiogenic agents and/or promote changes in the tumour vasculature.

The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In this Review, the authors describe the clinical potential of agents designed to inhibit the IL-6/JAK/STAT3 signalling pathway, either alone or in combination with other agents, in patients with cancer.

The safety of elective exogenous hormonal exposure among breast cancer survivors or women at high risk of having the disease has been debated for decades. Herein, the authors discuss the available data and present clinical recommendations regarding four areas of potential exogenous exposure to hormones: hormonal contraception; systemic hormone-replacement therapy; localized hormone-replacement therapy; and hormonal manipulation for fertility preservation or enhancement. Further research is needed to improve patient management in the future.

Both multiple myeloma and acute myeloid leukaemia are often preceded by defined precursor stages of neoplasia, which can aid efforts to unravel the mechanisms of disease progression. Herein, the authors review studies of the important roles of microenvironmental factors in promoting the development and progression of haematological cancers in these precursor conditions. Potential therapeutic strategies targeting the abnormal bone-marrow microenvironment are discussed.

Aberrant chromosomal architecture is one of the most common features of cancer and can often lead to chromosomal instability (CIN). In this Review, the authors describe the role of CIN in the development and progression of cancer and the potential to target the therapeutic vulnerabilities created by this process.