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In the randomized phase 1b/2 Morpheus-Melanoma trial evaluating various neoadjuvant immune checkpoint inhibitor regimens in patients with resectable stage III melanoma, tobemstomig, an anti-PD-1/anti-LAG-3 bispecific antibody, showed the highest pathologic response rate with a better safety profile than the standard treatment approach of ipilimumab plus nivolumab.

As life expectancy increases globally, psychotherapy for people aged 65 years and above must become more specialized and competent. In this Review, Laidlaw et al. describe findings from gerontological and psychological research that seek to improve mental health interventions in late life and enhance older adults’ emotional capabilities and motivations.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

HYPOMAP integrates single-nucleus RNA sequencing and spatial transcriptomic data to create a comprehensive spatio-cellular map of the human hypothalamus.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

A patient with newly diagnosed glioblastoma was safely treated with neoadjuvant nivolumab, relatlimab and ipilimumab before maximal resection, with comprehensive immune profiling showing the induction of overall immune activation early during treatment. The patient had no definitive evidence of recurrence at 17 months after treatment.

Clatworthy and colleagues examine adult nasal lymphoid tissues in response to SARS-CoV-2 infection. Longitudinal profiling reveals changes in barrier tissue to block viral entry beyond the epithelial cell layer and how tissue repair occurred after viral infection.

Analysis of data from multiple instruments reveals a giant exoplanet in orbit around the 0.2-solar-mass star TOI-6894. The existence of this exoplanetary system challenges assumptions about planet formation and it is an excellent target for atmospheric characterization.

Versluis et al. examine disease recurrence after initial pathologic response to neoadjuvant immune checkpoint inhibition in stage III melanoma. As no genetic changes in the tumor cells mediating immune evasion are found, it is proposed that disease recurrence may potentially be explained by diminishing of the initial therapy-induced immune response.

The connection between the molecular and physical control of embryonic tissues remains unclear. Here, the authors connect genetic mutations to changes in the physical state of posterior tissues during axis elongation, revealing a key role for dorsal tissues.

Since the publication of the first issue of Nature Reviews Clinical Oncology, we have witnessed advances in multiple research areas that have culminated in improved outcomes for many cancer types, although substantial unmet needs remain for a majority of patients worldwide. Here, we have asked experts in several key specialities to reflect on the progress from the past 20 years and propose the next steps to enable further advances. Although we are aware that this Viewpoint cannot provide full coverage of the vast field that is clinical oncology, we hope that these messages inspire a diverse range of readers.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during cancer progression.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A pooled analysis of neoadjuvant immunotherapy trials in melanoma shows that the degree of pathological response associates with patient survival and might represent a surrogate marker for long-term outcomes.

In this non-comparative trial, patients with BRAF^V600-mutant resectable melanoma received either pembrolizumab alone, a sequential combination of pembrolizumab, dabrafenib and trametinib, or a concurrent combination thereof, showing encouraging clinical response rates in the concurrent therapy arm and awaiting longer follow-up.

Using a globally distributed standardized aerial sampling of fungal spores, we show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude.

Georgina V. Long is co-medical director of Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research. She is the first woman president of the Society for Melanoma Research.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

The identification of prognostic biomarkers can help stratify cancer patients. Here, the authors apply deep RNA sequencing from primary melanomas coupled with long-term clinical outcome data from a prospective multicentre phase III trial, to develop and validate a 121 metastasis-associated gene signature identifying early-stage melanoma patients at higher risk of metastasis and worse survival.

Dimitriou et al. perform multiomic profiling of patients with melanoma experiencing immunotherapy-associated toxicity and identify a targetable role for type III-associated immune responses with an increase in CD4⁺ T cells expressing IL-17A.

In a post hoc analysis of the phase 2 PRADO trial, baseline emotional distress was associated with reduced clinical responses in patients with stage III melanoma treated with neoadjuvant ipilimumab and nivolumab.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Results from the PRADO extension cohort of the OpACIN-neo trial show that pathologic response rate to neoadjuvant ipilimumab and nivolumab can be used as a criterion for personalization of further treatment in stage III nodal melanoma, with the potential to reduce treatment morbidity and increase patient quality of life.

In an ongoing adaptive-design trial exploring different combinations of neoadjuvant immunotherapies including the anti-PD-1 agent pembrolizumab, the anti-TIGIT agent vibostolimab and the oncolytic virus gebasaxturev, neoadjuvant pembrolizumab-based regimens elicited encouraging clinical responses in patients with resectable melanoma.

Therapeutic resistance to immune checkpoint inhibitor treatment is incompletely understood in adolescent and young-adult (AYA) patients with melanoma. Here, the authors demonstrate that AYA patients exhibit a unique stroma-infiltrating T cell immunogenomic profile compared with adults, which impacts on their responsiveness to immunotherapy.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Neolithic farming practices differed across the Mediterranean. Here, the authors apply a machine learning approach to combined archaeological and paleoclimatic data, investigating the impact of climate on the spread of agriculture in the Mediterranean.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

In this pre-specified interim analysis, patients with resected stage IIB/C melanoma who received adjuvant nivolumab had significantly prolonged recurrence-free survival compared to placebo-treated patients, providing another treatment option for this population.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Anaerobic methanotrophic archaea play crucial roles in the methane cycle. Here, Zhang et al. provide experimental evidence supporting that multi-heme cytochromes mediate extracellular electron transfer for the reduction of metals and electrodes in these microorganisms.

A global gauge-corrected monthly river flow and storage dataset suggests that residence time is a key driver of water storage and variability and indicates substantial freshwater discharge to the ocean from the Maritime Continent.

Multi-ancestry genome-wide association meta-analysis of major depression identifies new risk loci, assesses the transferability of risk loci across ancestry groups, and improves fine-mapping resolution and prioritization of candidate effector genes.

A computational framework draws analogy with foams to offer a comprehensive picture of how cell behaviours influence fluidization in embryonic tissues, highlighting the role of tension fluctuations in regulating tissue rigidity.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The radial-velocity technique could detect a small gas giant orbiting a binary star and determine its mass: 65.2 ± 11.8 Earth masses. The system also hosts a smaller inner planet, making it one of the few known multiplanetary circumbinary systems.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.