Reviews & Analysis

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.

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.

Major advances in our understanding of the molecular pathogenesis of non-small-cell lung cancer (NSCLC) have led to effective targeted therapeutics in several genomically-defined subsets of NSCLC. The recently updated College of American Pathologists, International Association for the Study of Lung cancer, and Association for Molecular Pathology joint guideline, which was endorsed by ASCO, sets new standards for molecular testing in NSCLC.

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 biological complexity of triple-negative breast cancers (TNBCs) and the lack of highly recurrent targetable genetic alterations pose major challenges for the implementation of targeted therapies for this disease. A recent multiomic in silico study has identified genetic drivers of five different TNBC molecular subtypes, providing new opportunities for precision medicine approaches.

Patients with solid tumours can have unusual patterns of response to anticancer immunotherapy, necessitating the adaptation of traditional response criteria. A recent retrospective analysis of data from patients with four different types of solid tumours treated with the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab confirms the previous experience in patients with melanoma and provides several new insights.

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 aberrant tumour vasculature and the associated angiogenic factors have been implicated in tumour immune evasion and progression. Herein, the authors provide their perspectives on how normalization of the tumour microenvironment using antiangiogenic agents could potentially increase the effectiveness of immunotherapies and improve the outcomes of patients with cancer. The authors also highlight important considerations for future research in this area.

Despite the rising incidence of cancer in low-income and lower-middle-income countries, very few oncologists are present in these regions — or, in some areas, even none. However, limited evidence of the global oncology workload inequity is available in the literature. Herein, we summarize recent findings that shed some light on this problem and discuss potential oncology workforce solutions.

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.

Patients value anticancer therapies that provide durable clinical responses; immune-checkpoint inhibitors can provide such benefit for patients with some advanced-stage malignancies, albeit only for a minority of those treated. Modern oncology value frameworks have set efficacy thresholds in an attempt to assess the clinical benefit of anticancer therapeutics. But, is the benefit of durable cancer control reflected in these thresholds?

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.

Recently published data from a large-cohort study confirm the substantial burden of chronic health conditions among childhood cancer survivors, and describe the multiple chronic conditions faced by these individuals. The findings emphasize the need for specialized care in this unique patient population that, as discussed herein, often goes unmet. More must be done to ease the burden on cancer survivors; new models of care are required to improve their long-term health.

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.