Reviews & Analysis

The oligometastatic state is generally considered to constitute an intermediate point along the spectrum of cancer dissemination at which the metastatic burden is limited and local ablative therapies can result in meaningful clinical benefit, and possibly even cure. In this Review, Katipally et al. reframe the oligometastatic phenotype as a dynamic state that expands beyond merely the number or size of metastases. They highlight important risk factors defining the metastatic spectrum that can inform both staging and therapy, and identify themes in the literature that might guide strategies to optimally combine metastasis-directed local therapies with modern systemic treatments.

Tracking circulating tumour DNA (ctDNA) after surgery holds promise for patient management and therapeutic intervention in non-small-cell lung cancer (NSCLC). A study published by Zhang and colleagues tracks ctDNA from 261 patients with stages I–III NSCLC and suggests that the likelihood of disease relapse decreases for high-risk stage II/III patients after 18 months without ctDNA detection.

After a frustratingly slow pace of development of new effective treatments for mesothelioma, single or dual therapy with immune-checkpoint inhibitors has substantially improved overall survival over previous standard-of-care therapies in various disease settings. The authors of this Review summarize the current evidence on immunotherapies for mesothelioma, focusing on strategies evaluated in randomized clinical trials and emerging predictors of response, and discuss future treatment opportunities.

Liquid biopsy assays of diverse cancer-associated molecular alterations in blood, including genomic, epigenomic, transcriptomic, proteomic and metabolomics changes, offer considerable opportunities for early detection of cancer as well as improved management of the disease. In this Perspective, the authors review key advances in liquid biopsy-based multi-omics approaches for biomarker discovery. They also introduce the ‘nano-omics’ paradigm, whereby nanotechnology tools are used to capture and enrich various cancer-derived analytes from biofluids for subsequent omics analyses, with the aim of developing novel biomarker panels for early cancer detection.

Radiotheranostics enables the clinician to image and then target lesions using the same probe. Despite this appealing potential, interest in the field of radiotheranostics has long been constrained by a lack of expertise, high infrastructure costs and the availability of non-radioactive alternative approaches. Nonetheless, several recent successes have led to renewed research interest. In this Review, the authors summarize the current challenges and opportunities in this rapidly emerging area.

A recent study not only confirms mounting evidence that technology-facilitated symptom monitoring improves care and should be considered for all patients with cancer, but also suggests that patient navigators can help to deliver such interventions. Herein we discuss how such an approach can minimize disparities and maximize access to culturally appropriate patient-centred care.

Neuroblastomas are tumours of sympathetic origins typically seen in infants (≤5 years of age). In this Review, the authors describe progress in the treatment of patients with neuroblastoma, which has resulted in considerable improvements in survival outcomes over the past several decades. The authors then summarize ongoing attempts to personalize therapy in patients with high-risk disease, and to safely de-escalate therapy in those with low-risk disease.

Immune-checkpoint inhibitors have revolutionized the treatment of patients with non-small-cell lung cancer (NSCLC). Recently, indications for immune-checkpoint inhibitors have expanded from advanced-stage NSCLC to adjuvant, and now neoadjuvant, therapy for resectable NSCLC, with three cycles of preoperative chemoimmunotherapy achieving superior pathological complete response rates and event-free survival compared with chemotherapy alone in the phase III CheckMate 816 trial.

Patients with non-small-cell lung cancers (NSCLCs) harbouring oncogenic EGFR or ALK alterations can benefit from therapies targeting these alterations, although acquired resistance to these agents is common. Third-generation inhibitors have extended the response durations of many patients with NSCLCs harbouring these alterations, albeit with differing patterns of resistance to those associated with earlier-generation agents. Here, the authors describe the mechanisms of acquired resistance to third-generation EGFR and ALK inhibitors and provide insights into future research directions in this area.

Several PI3K pathway inhibitors are currently approved as cancer treatments; however, finding an acceptable therapeutic window to target this key signalling cascade linking cancer growth with metabolism has proven challenging and the clinical results to date have arguably been disappointing. In this Review, Vasan and Cantley discuss the effects of PI3K pathway alterations on signalling and metabolism in solid tumours as well as past and present efforts to improve the somewhat limited clinical efficacy of PI3K pathway inhibitors, with a particular focus on PI3Kα in breast cancers.

In this Perspective, Nathan Cherny appraises the FDA approvals of therapeutic agents granted for use in adult patients with solid tumours during the 5 years 2017–2021 against the aspirations of the Cancer Moonshot, in terms of sheer number of approvals, the strength of the supporting evidence and the magnitude of clinical benefit. He also outlines areas where improvements are needed to more confidently ensure that the clinical benefits of approved treatments justify the associated risks.

Immune-checkpoint inhibitors and BRAF-targeted therapy have revolutionized the treatment of advanced-stage, unresectable melanoma and have been successfully transitioned into the resectable disease setting as (neo)adjuvant treatments. The expanding range of treatment options available for resectable high-risk melanoma raises questions over selection of the optimal therapeutic strategy and agents for each individual. Furthermore, the use of perioperative therapy has potentially important implications for the management of patients who have disease recurrence. In this Viewpoint, we asked four expert investigators who have been involved in the key studies of perioperative systemic therapies for their perspectives on the optimal management of patients with high-risk melanoma.

Two recent large-cohort studies reinforce the potential predictive capability of gut microbiota for immune-checkpoint inhibitor response and toxicities in patients with melanoma. However, additional investigations are required to understand the mechanistic underpinnings of this complex multifaceted relationship, and how it can be exploited for personalized cancer care.

In the past decade, treatment devices that combine imaging with targeted irradiation have been developed to deliver MRI-guided radiotherapy (MRIgRT). This treatment modality uses motion management and biological targeting to improve local control rates whilst reducing the radiation delivered to non-malignant tissues. The authors of this Review describe the current state of MRIgRT, and the opportunities and challenges of this radiotherapy approach.

To achieve health equity, we advocate for the overrepresentation of particular racial and ethnic minority groups so that analyses of group-specific treatment effects can be optimally powered. A paradigm shift is needed across multiple stakeholders, as well as in the engagement of community programmes, the role of investigators from racial and ethnic minority backgrounds and clinical trial regulations.

The tumour microenvironment includes various diverse immune cell types, each of which might influence tumour progression and response to treatment, particularly with immunotherapies. These cell types include different subtypes of B lymphocytes, which are often associated with tertiary lymphoid structures (TLS) and can have pro-tumour or anti-tumour effects, either through their classical function in antibody production and antigen presentation or other mechanisms. Herein, Fridman et al. discuss the phenotypic heterogeneity of intratumoural B cells and the importance of TLS in their generation, the potential of B cells and TLS as prognostic and/or predictive biomarkers, and novel approaches aiming to enhance the development of TLS and anti-tumour B cells for cancer therapy.

The interaction of tumour-associated macrophages (TAMs) with cancer and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. The authors of this Review examine the diversity of TAMs in various cancer indications, which is being revisited with the advent of single-cell technologies, and discuss the functional roles of different TAM states, the prognostic and predictive value of TAM-related signatures as well as approaches involving TAMs that are currently being or will soon be tested in clinical trials.

Over the past decade, iterative improvements to models predicting breast cancer risk have primarily come from new information about genetic risk factors and improvements to mammogram-based risk scores. Epigenetic risk factors offer some potential to further improve risk stratification. However, the recently developed DNA methylation score (the WID-BC index) is not yet convincing for predicting breast cancer risk.

Non-small-cell lung cancer (NSCLC) is a growing public-health threat, with one of the highest mortality risks among non-communicable diseases. Now, researchers have developed a diagnostic tool for NSCLC by mass spectrometry of a targeted panel of lipids. Herein, we discuss key aspects that could facilitate the clinical implementation of this and similar tools in other fields of application.

Photoacoustic imaging is a novel imaging technique that provides scalably high levels of spatial resolution at rapid acquisition speed, without the need for radiation or exogenous contrast agents. In this Review, the authors describe the emerging role of this technology in the screening, diagnosis and management of patients with cancer, and provide an overview of the future implementation of this technology.