Reviews & Analysis

Studies have identified multiple molecular properties with a biological rationale supporting a role in mediating selective responses to immune-checkpoint inhibitors (ICIs), including loss-of-function mutations in mSWI/SNF chromatin regulators; however, their clinical biomarker relevance is uncertain. Herein, we evaluate emerging concepts, challenges and considerations around translating biology into biomarkers for ICIs in solid tumours setting.

Herein, the European Association of Neuro-Oncology (EANO) provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials.

The availability of ever more sensitive cell sorting and sequencing technologies has enabled the interrogation of tumour cell biology at the highest possible level of resolution — analysis of a single cell. In this Perspective, the authors describe the application of such approaches to the analysis of single tumour-associated immune cells and their potential for improving the outcomes in patients receiving anti-cancer immunotherapies.

The much anticipated results from two phase III studies evaluating the clinical efficacy of poly(ADP-ribose) polymerase (PARP) inhibition in patients with advanced-stage breast cancer harbouring a germline mutation in BRCA1/2 have established new therapeutic opportunities and yet, have left us with several ongoing questions.

Opposing results of the monarchE and PALLAS trials investigating the role of adjuvant treatment with the CDK4/6 inhibitors abemaciclib and palbociclib, respectively, in patients with hormone receptor-positive, HER2-negative early stage breast cancer have recently been presented. Herein, potential reasons why these two drugs that have similar efficacy in the metastatic setting have produced disparate results in the adjuvant setting are discussed.

The incidence of early-onset colorectal cancer (CRC) is increasing worldwide for reasons that are currently unclear. Herein, the authors review the current epidemiological, clinical, pathological and molecular understanding of early-onset CRC that occurs in patients ≥50 years of age, drawing contrasts with later-onset CRC. They also discuss future research strategies for improved understanding, prevention, early detection and clinical management of early-onset CRC.

Nuclear import and export proteins, such as exportin 1(XPO1), regulate the transport of proteins and other molecules into and out of the nucleus, including several tumour suppressor proteins. The dysregulation of nuclear export can be observed in several types of haematological and solid tumours, providing a rationale for a novel form of targeted therapy. In this Review, the authors describe the development of XPO1 inhibitors, from basic research to clinical approval.

Noninvasive liquid biopsy assays integrating tumour and immune biomarkers are a promising tool to enhance clinical decision-making in immuno-oncology. Here, we discuss how circulating tumour DNA dynamics, in conjunction with pre-treatment tumour and immune features, can predict clinical response to immune-checkpoint inhibitors alongside the challenges in making their use a clinical reality.

Randomized controlled trials designed to test cancer therapies often fail to clarify effectiveness in real-world settings. Herein, we explore lessons for trial development in oncology that can be learnt from the large-cohort, pragmatic RECOVERY trial involving patients hospitalized with COVID-19.

We argue that the evidence remains insufficient for use of intraoperative radiotherapy (IORT) in women with early stage breast cancer outside of a clinical trial, as the recently reported TARGIT-A trial does not provide sufficient evidence to conclude that IORT is superior to no radiotherapy.

Despite the introduction of novel therapies, lung cancer remains the leading cause of cancer-related mortality worldwide. Randomized controlled trials of low-dose CT-based lung cancer screening in high-risk populations have shown a reduction in mortality. The authors of this Review discuss these studies and present the Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL), a framework to define the scope of future implementation research on lung cancer screening.

Tumour-associated antigens are an attractive therapeutic target in immuno-oncology. Here, the exploratory analyses of T cell responses and preliminary clinical outcomes of the Lipo-MERIT trial of a melanoma vaccine are discussed in the context of prior efforts to harness the immunogenicity of such antigens for antitumour immunity.

Despite several major therapeutic advances, multiple myeloma (MM) remains largely incurable, indicating a need for novel therapies. Thus, considerable research interest exists in chimeric antigen receptor (CAR) T cells targeting BCMA, which is almost universally expressed on MM cells. In this Review, the authors describe the clinical experience with anti-BCMA CAR T cells and discuss several new directions of future research that might prolong the responses of patients receiving these therapies.

Technological advances have enabled the analysis of whole genomes, leading to the identification of causal factors that present new opportunities to prevent cancer. The authors of this Review discuss relevant findings in cancer genetics and genomics from the perspective of global cancer prevention and present a conceptual framework for the translation of such findings into clinical practice and evidence-based policies.

A role for extracellular vesicles and particles (EVPs) as cancer biomarkers has been elusive. A mass spectrometry-based comparative analysis of EVPs from individuals with or without cancer has now enabled the identification of tumour-associated protein profiles in EVPs in plasma and paired tumour tissues, validating the role of EVPs as a novel liquid biopsy approach in cancer diagnosis.

Natural killer (NK) cells have an innate potential to kill cancerous cells and considerable effort is being focused on innovative approaches to leverage these cells for cancer therapy. Herein, the authors discuss the variety of NK cell-based therapies that are being developed for the treatment of diverse cancers and identify future avenues for NK cell therapy research.

Genotyping is recommended for all patients with metastatic non-squamous non-small-cell lung cancers (NSCLC), both to enable patients to receive targeted therapies and to avoid therapies they are unlikely to benefit from. However, obtaining tumour biopsy material for genotyping is often challenging and is unfeasible in some patients, indicating the need to incorporate liquid biopsy approaches. In this Perspective, the authors provide guidance on how analysis of ctDNA from liquid biopsy samples in patients with metastatic NSCLC prior to first-line therapy has the potential to extend the benefits of genotyping to virtually all patients.

Tumour budding is hypothesized to reflect the invasive and metastatic capacities of cancers and is accordingly associated with unfavourable patient outcomes. Herein, Lugli and colleagues describe the pathobiological characteristics of this phenomenon, including its associations with epithelial–mesenchymal transition and features of the tumour microenvironment, and review the evidence demonstrating the value of tumour budding as a prognostic biomarker across various solid cancers.

The number of adults aged ≥65 years with cancer is rapidly growing; these individuals continue to have worse outcomes than younger adults with cancer. The authors of this Review summarize the unique challenges of treating older adults with cancer owing to competing health and ageing-related conditions, and describe the current guidelines as well as investigational studies underway to improve the outcomes of these patients.

The possible uses of artificial intelligence (AI) in radiation oncology are diverse and wide ranging. Herein, the authors discuss the potential applications of AI at each step of the radiation oncology workflow, which might improve the efficiency and overall quality of radiation therapy for patients with cancer. The authors also describe the associated challenges and provide their perspective on how AI platforms might change the roles of radiation oncology medical professionals.