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  • 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.

    • Lois Gardner
    • Kostas Kostarelos
    • Marilena Hadjidemetriou
  • 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.

    • Lisa Bodei
    • Ken Herrmann
    • Jason S. Lewis
    Review Article
  • 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.

    • Gabrielle B. Rocque
    • Abby R. Rosenberg
    News & Views
  • 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.

    • Bo Qiu
    • Katherine K. Matthay
    Review Article
  • Timely and comprehensive updating of treatment guidelines remains a challenge and necessity in medical oncology. Herein we discuss our assessment of how trial results with four off-patent drugs have been considered for integration into major guidelines in the absence of a commercial sponsor, in which we found reasons for concern.

    • Gauthier Bouche
    • Lydie Meheus
  • 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.

    • Boris Sepesi
    • Stephen G. Swisher
    News & Views
  • 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.

    • Alissa J. Cooper
    • Lecia V. Sequist
    • Jessica J. Lin
    Review Article
  • 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.

    • Neil Vasan
    • Lewis C. Cantley
    Review Article
  • 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.

    • Nathan I. Cherny
  • 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.

    • Alexander M. M. Eggermont
    • Omid Hamid
    • Jason J. Luke
  • 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.

    • Neal Bhutiani
    • Jennifer A. Wargo
    News & Views