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In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

Kroemer and colleagues discuss evidence supporting the importance of immunosurveillance in natural and therapy-induced killing of breast tumors.

Trastuzumab deruxtecan, an anti-HER2–drug conjugate, exhibits the highest objective response rate in patients with HER2-overexpressing metastatic breast cancer, but clinical activity is also observed in patients with HER2-low or non-expressing tumors, potentially pointing to additional determinants of drug efficacy.

The Q-cycle is thought to be an essential energetic component of the photosynthetic electron-transfer chain. Here, Chlamydomonas mutants with an inactive Q-cycle but normal levels ofb₆fcomplexes are shown to display photosynthetic growth, demonstrating the dispensability of the Q-cycle in the oxygenic photosynthetic chain.

Borcoman and colleagues present the efficacy and safety results of the phase 2 PEVOsq basket trial investigating the combination of pembrolizumab with the epidrug vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma.

Targeted therapies matched to genomics improved progression-free survival when genomic alterations were classified as level I/II (according to ESCAT), and genomics should thus be driven by target actionability in patients with metastatic breast cancer.

Barlesi and colleagues describe the determinants of severe COVID-19 outcomes in patients with cancer managed at the Gustave Roussy Cancer Centre.

Patient data from six clinical trials are used to compare the genomic landscapes of breast cancer metastases with those of primary tumours, revealing an increase in mutational burden and clonal diversity.

“In subarachnoid hemorrhage (SAH), therapies are limited and clinical outcomes remain disappointing. The authors show a contribution of the urotensin II system in microvascular changes, vasospasm, neuroinflammation and cognitive deficits post-SAH, primarily through meningeal cells and border-associated macrophages

In this prespecified interim analysis of the KEYNOTE-756 phase 3 trial, pembrolizumab and chemotherapy treatment of patients with high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor-negative breast cancer improved the pathological complete response rate compared with chemotherapy alone.

In high light conditions, terrestrial plants dissipate excess energy as heat. However, microalgae such as Chlamydomonas use state transitions, not to dissipate excess light energy, but to efficiently redistribute it between the photosystems.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Yellow fever is a public health threat in the Americas but has not recently been reported in the Caribbean despite presence of the mosquito vector Aedes aegypti. Here, the authors show through experimental infection that populations of Aedes aegypti from the Caribbean and surrounding areas are competent of yellow fever transmission.

Devices that harness electron flow from photosynthetic organisms generally compromise host photosynthesis. Here, the authors show that, by redesigning the Q_Asite of Photosystem II, it is possible to reroute electrons to an exogenous quinone while maintaining endogenous photosynthetic electron transfer in a green alga.

Metastasis of urothelial carcinoma remains incurable due to insufficient treatment options for advanced disease. Here, the authors combine whole exome sequencing and RNA-seq from metastatic biopsies, and show temporal evolution when compared with primary tumour.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

The complexity of spatial omics data presents analytical challenges and demands substantial computing resources. Here, the authors introduce Sopa, a technology-invariant, memory-efficient pipeline with a unified visualizer for all image-based spatial omics.

The switch from linear to cyclic electron flow has long been thought to rely on the migration of antenna proteins from Photosystem II to Photosystem I. Takahashi et al. report that this is not the case and that cyclic electron flow is tuned by the intrachloroplastic redox power.

There is much concern in the literature over the lack of reproducibility of many scientific reports. In this Perspective, the authors discuss how cognitive biases in research and flaws in the academic incentive system also contribute to the publication of immature results. The authors suggest some changes to the grant submission and funding system that could further improve the reproducibility of research findings.

Current preclinical models to investigate human HR + breast cancer progression and response to immunotherapy in vivo are limited. Here, the authors demonstrate that mammary tumours driven by a synthetic progestin combined with an oral carcinogen recapitulate several immunobiological features of human HR + breast cancers.

Several guidelines propose the use of Ki67 expression to select which patients with early stage breast cancer and 1–3 positive nodes should not receive adjuvant chemotherapy. In this Perspective, the authors discuss why, in 2015, the oncologist should not rely on the use of this biomarker for decision-making in this patient population—owing to lack of analytical validity of Ki67 staining, its poor performance for prognostic purposes, and no strong evidence indicating that Ki67 staining predicts the efficacy of adjuvant chemotherapy.

Charge-transfer dynamics in organic semiconductors are shown to be altered by multi-layered hyperbolic metamaterial substrates, an effect linked to the number of metal–dielectric pairs used.

Anthracyclines can induce a type 1 interferon response in tumor cells that may predict clinical response to these drugs.

The conventional way of classifying metastatic cancers according to their organ of origin is denying people access to drugs that could help them.

Half of the population of Central Amazon river-floodplain communities are subject to an unstable riverscape, according to an assessment of compound risk which integrates environmental hazard observations with regional socio-economic information.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.

Exploratory analyses from the phase 2 randomized SAFIR02-IMMUNO trial identify biomarkers associated with improved outcomes to durvalumab as compared to maintenance chemotherapy in patients with triple-negative breast cancer.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

An important contribution of cancer associated fibroblasts (CAFs) in regulating chemoresistance has been reported. Here the authors investigate the impact of chemotherapy on CAF subsets in patients with high-grade serous ovarian cancer, suggesting that residual ANTXR1+ myofibroblasts are associated with inhibition of anti-tumor immunity.

Chromosomal instability enables the continuous selection of somatic copy number alterations, which are established as ordered events that often occur in parallel, throughout tumour evolution and metastasis.

Melanoma persister cells are tolerant to anti-BRAF and anti-MEK inhibition and can trigger cancer relapse. Here the authors show that a subset of N6-methyladenosine modified mRNAs is translationally activated in persister cells. This preferential translation can be abrogated via eIF4A inhibition.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Flexible organic electronics operated at extreme mechanical conditions are crucial for the next generation of smart foldable electronic applications. Kim et al.show non-volatile organic memory devices that are subject to sharp bending deformation without protection from a stress-release layer.