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Regulatory approval of new cancer medicines can have important consequence for patients with advanced-stage and/or rare cancers who have exhausted all standard-of-care therapies. However, evidence that new medicines are safe and effective can also take time to accrue, and approval with a lack of evidence may cause unnecessary harm to patients. In this Viewpoint, we asked two leading oncologists involved in clinical drug development, an expert in regulatory science and prescription drug policy, and a prominent patient advocate, to provide their opinions on the current approach to cancer drug approvals.

Professional antigen presenting cells (APCs) are deterred from phagocytosing cancer cells that express CD47. Here, the authors show that in glioblastoma mouse models, temozolomide improves the phagocytosis effect of CD47 blockade in APCs and results in the activation of adaptive anti-tumour responses.

Here, the authors report that METTL3 orchestrates cellular senescence by coordinating its enzymatic activity-dependent and independent functions. METTL3-mediated chromatin loops induce phase separation via metabolic reprogramming.

The small GTPase ARF6 is known to regulate endocytosis and recycling of plasma membrane proteins. Here the authors show that tumourintrinsic ARF6 promotes an immunosuppressive microenvironment that accelerates melanoma progression but that is vulnerable to immune checkpoint blockade, mechanistically linked to ARF6-dependent recycling of interferon-gamma receptors in tumour cells.

Genomic and transcriptomic analysis of 393 non-small cell lung cancer patients treated with checkpoint inhibitors identifies molecular features associated with response.

EPIC-seq predicts expression of individual genes from cell-free DNA.

This study, together with a companion manuscript, show that, in mice, weight loss as a result of GIP receptor antagonism requires, and potentiates, functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

A World Health Organization (WHO) advisory committee meeting in Geneva at the end of last month approved phase III trials for HIV vaccines in developing countries. What is the justification for this decision?

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Electronic rotons and Wigner crystallites have been observed experimentally and numerically in a two-dimensional dipole liquid.

Iron deficiency is the leading cause of anaemia and is known to compromise immune function. Here, the authors identify several new genes associated with iron status in European populations and provide insight into how iron levels may be linked to the risk of metabolic disease.

Early life exposure to environmental stressors, including endocrine disrupting chemicals (EDCs), can impact health later in life. Here, the authors show that neonatal EDC exposure in rats causes epigenetic reprogramming in the liver, which is transcriptionally silent until animals are placed on a Western-style diet.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

High-density integration will be vital for silicon photonics, but as we approach sub-wavelength distances between components, the crosstalk becomes intolerable. Here, Song et al. demonstrate waveguide integration at a half-wavelength pitch with low crosstalk using advanced superlattice design concepts.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

Noncoding transcripts contribute to the adaptation of cellular processes to oxygen levels. Here the authors characterize a hypoxia responsive lncRNA lincNORS and show that it has a role in cellular sterol homeostasis.

Hata and colleagues identify lorlatinib analogs that overcome acquired therapy resistance to current ALK inhibitors and show their efficacy in preclinical models of non-small cell lung cancer bearing compound therapy-resistant ALK alterations.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

Coupling strengths differ between neighbours in square artificial spin ices, resulting in the loss of degeneracy. Introducing mesospins on vertices of the array alleviates this problem, by tuning the strength and ratio of the interaction energies.

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

A general theoretical technique is introduced to identify materials that host flat bands. Applying topological quantum chemistry provides the generating bases for these flat bands in all space groups.

The development of single-molecule electronics calls for precise tuning of the electronic properties of individual molecules that go beyond two-terminal control. Here, Wickenburg et al. show gate-tunable switch of charge states of an isolated molecule using a graphene-based field-effect transistor.

In a randomized phase 3 trial, the combination of the BET inhibitor pelabresib with the JAK inhibitor ruxolitinib resulted in a significantly higher spleen volume reduction from baseline versus placebo with ruxolitinib in patients with JAK inhibitor-naive myelofibrosis.

Neoadjuvant pembrolizumab promotes a survival benefit with intratumoral and systemic immune responses in patients with recurrent glioblastoma.

Although Hippo signaling restricts regeneration in many mammalian organs, the pharmaceutical tools available to modulate the pathway have been limited. Here, the authors report a small molecule that may inhibit a key element in the Hippo cascade and may activate regenerative responses in several mammalian tissues.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

Analysis of a fossil trackway from the earliest Carboniferous of Australia shows prints of toes with claws, suggesting that the origin of amniotes was at least 35–40 million years earlier than previously thought.

Bar-Eli and colleagues report that CREB-mediated downregulation of the RNA-editing enzyme ADAR1 results in decreased adenosine-to-inosine editing of miR-455-5p, which enhances melanoma growth and metastasis.

There is increasing interest in measuring the mechanical properties of living cells. Here, the authors develop a method to simultaneously measure the cell mass and two parameters related to its natural oscillation or resonance frequencies.

Rapid extracellular antibody profiling reveals a contribution of autoantibodies to the effectiveness of checkpoint immunotherapy for cancer.

This study shows that animal-based high-fat diets accelerate tumour growth and impair anti-tumour response to melanoma in obese mice, whereas plant-based high-fat diets do not.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.

Cancer cells have altered lipid metabolism. Here the authors show that DAXX promotes lipogenesis and tumorigenesis through interaction with SREBP1/2.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Anderson localization is a disorder-driven phenomenon typically considered in the context of low-temperature condensed-matter systems. However, the phenomenon can also be relevant to soft matter and here the authors experimentally demonstrate it is possible to observe Anderson localization of ultrasonic waves in soft matter doped with resonant encapsulated microbubbles.

Oblique line scan microscopy achieves nanoscale spatial and sub-millisecond temporal resolution across a large field of view, enabling improved and robust single-molecule biophysical measurements and single-molecule tracking in both cells and solution.

An individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA-based neoantigen vaccine is safe and well tolerated in patients, warranting further studies to test its potential to rescue response to checkpoint blockade in tumors of low immune reactivity.

“Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. Here the authors show that PopZ condensate dynamics support cell division and using PopZ modular architecture, the tunable PopTag platform was developed to enable designer condensates.”

An optically addressable fluorescent-protein spin qubit is realized using enhanced yellow fluorescent protein; the qubit can be coherently controlled at liquid-nitrogen temperatures and the spin detected at room temperature in cells.