We thank Wu et al. for their comments on our Review (Peuget, S., Zhou, X. & Selivanova, G. Translating p53-based therapies for cancer into the clinic. Nat. Rev. Cancer 24, 192–215 (2024))1; they raise some interesting points that we respond to below (Wu, J., Song, H., Xiao, S. & Lu, M. Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies. Nat. Rev. Cancer https://doi

Melanoma exhibits distinct patterns of organ-specific spread. Now, Gurung et al. find that age-based variations in stromal lipid species dictate melanoma metastatic tropism to the liver.

In addition to its physical symptoms, cancer cachexia — a severe wasting syndrome — also leads to fatigue, apathy and depression. A recent study published in Science identifies neural circuit mechanisms that underlie these motivational symptoms.

In this Journal Club. Gupta and Das discuss a study demonstrating how Apc-deficient intestinal stem cells (ISCs) gain a competitive advantage over normal ISCs through the upregulation of NOTUM.

In this Tools of the Trade article, Xinyuan Bi describes the development of digital colloid-enhanced Raman spectroscopy (dCERS), a method that addresses the reproducibility issues of surface-enhanced Raman spectroscopy (SERS) at ultra-low concentrations by using single-molecule counting.

Ali Sonay describes the development of an image-guided surgical approach that uses a commercially available dye, CJ215, to improve the real-time detection and precise removal of cancerous tissues and for better preclinical visualization of cancer progression in deep tissues.

In this Journal Club, Dimple Notani discusses a study that demonstrates a tumour suppressive function of the androgen receptor in oestrogen receptor-positive breast cancer.

In this Tools of the Trade article, Clare Puttick describes the development of MHC Hammer, a computational tool that uses whole-exome sequencing and RNA sequencing data for measuring HLA disruption.

In this Tools of the Trade article, Christopher Lowden describes the development and use of CRISPR-StAR, which leverages internal controls to overcome experimental noise for improved in vivo functional genomic screens.

In this Tools of the Trade article, Bercin Cenik describes the development and use of TurboCas, an enzyme that pairs catalytically dead Cas9 with the proximity-labelling enzyme miniTurbo to map the regulatory proteins that shape transcription.

The mechanisms of how pH-dependent cell death, alkaliptosis, is regulated are incompletely understood. Chen et al. now demonstrate that the cholesterol biosynthesis protein CYP51A1 suppresses alkaliptosis induced by the opioid analgesic JTC801.

In this Tools of the Trade article, Ziwei Xue describes the development and use of scAtlasVAE, a deep learning framework that integrates single-cell RNA-sequencing data from CD8+ T cells across studies.

Glycolysis-dependent T cell function is hindered by glucose scarcity in the tumour microenvironment. Now in Cancer Cell, Schild et al. engineered T cells to utilize fructose via GLUT5, enhancing their metabolic activity and cytotoxicity.

In this Tools of the Trade article, Kenta Ninomiya describes the development of ImAge, an imaging-based approach that captures age-related trajectories of chromatin and epigenetic marks in single nuclei for longitudinal analyses.

Understanding the complex relationship between ageing and cancer is crucial for cancer risk prediction. Here, we explore how tissue-specific ageing biomarkers can enhance cancer risk stratification and highlight the need for tailored approaches in assessing susceptibility across different tissues. Understanding the complex relationship between ageing and cancer is crucial for cancer risk prediction

Targeting metabolic dependencies, such as glucose or lipid metabolism, is a key strategy for anti-cancer therapies. Nguyen et al. developed a new approach, adipose manipulation transplantation (AMT), in which engineered adipocytes are used to outcompete tumours for lipids and glucose to suppress cancer progression.

A recent study published in Nature finds that neuroendocrine small-cell lung cancer (SCLC) cells exhibit electrical activity that directly drives tumour progression and metastasis and shows that they rely on oxidative phosphorylation to meet the high energy demand associated with these electrophysiological processes.

Yang et al. developed a proteolysis-targeting chimera (PROTAC) 753b, which targets BCL-xL and BCL-2 to the E3 ubiquitin ligase VHL, and showed that it removed senescent cells specifically from the liver, reducing the progression of chronic metabolic liver disease to liver cancer.

In this Tools of the Trade article, Jordan Lee describes the development and use of the Tumor Molecular Pathology (TMP) toolkit, a cancer subtyping tool that can assign TCGA molecular subtypes to new, independent non-TCGA datasets.

Wildfires release a range of known human carcinogens and tend to occur in the same regions each year. As a result, long-term exposures to wildfire pollutants are a concern and will probably increase cancer risk in exposed populations. Actionable solutions are available to reduce exposures and mitigate these risks. Wildfires emit carcinogenic pollutants, raising long-term cancer risks in affected populations

Advancements in cancer treatment have led to a growing population of cancer survivors worldwide, who often experience premature onset of age-related conditions. Understanding the molecular and cellular basis of the long-term consequences of cancer treatment is essential for developing interventions to mitigate their adverse effects. While cancer treatments are essential for patient survival, they often

In this Tool of the Trade article, Tim Coorens describes the development of SComatic, an algorithm enabling the detection of somatic mutations in single-cell RNA- or ATAC-sequencing data, and its use to study lineage relations and mutational signatures.

In this study, Alexander et al. find that HIF2α regulates speckle–DNA associations to fine-tune the expression of a subset of its target genes, and demonstrate that speckle phenotypes correlate with outcomes in renal cell carcinoma.

Immunosuppression disrupts normal skin homeostasis, raising the risk of cancer development. Now, Son et al. find that commensal papillomavirus maintains homeostasis in sun-damaged skin.

In a recent study published in Nature, Zhuang et al. outline how ageing affects stemness and tumorigenic potential of tumour-initiating alveolar stem cells in the lung.

The mechanisms by which dietary fructose promotes tumour progression have remained poorly understood. A recent study published in Nature reveals that dietary fructose is metabolized in the liver, resulting in elevated circulating lipid levels that can serve as building blocks for cancer cells outside the liver.

Intercellular mitochondrial transfer via tunnelling nanotubes can influence cellular bioenergetics and function in tumours. A study in Cell demonstrates how this process can increase CD8+ T cell metabolic fitness and anti-tumour function.

Wang et al. demonstrate that lactate derived from glioblastoma stem cells, microglia and macrophages drives histone lactylation, activating immunosuppressive transcriptional programs and upregulating CD47, to suppress phagocytosis.

In this Journal Club, Chakrabarti discusses a method to dissect the molecular architecture of inheritable gene expression (memory) states that mark cells that transition into drug-tolerant persister cells in melanoma.

The incidence of early-onset cancers has increased by approximately 80% over the past three decades. These patients have unique needs. For optimal care, designated OncoYoung programs should be created. In addition, multinational platforms with dedicated funding are necessary to investigate the aetiology of early-onset cancers and develop preventive measures. In this Comment, Ben-Aharon et al. advocate