Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Schulze and colleagues discuss the latest advances in understanding the role of lipids in cancer progression and metastasis and reflect on opportunities to target lipid metabolism in tumors.
Chromosomal instability (CIN) (a hallmark of human cancer) is caused by persistent errors in chromosome segregation during mitosis. Pharmacological inhibition of the mitotic kinesin KIF18A selectively exploits a mitotic vulnerability for which cancer models with CIN are enriched, which leads to robust anti-cancer effects and durable tumor regression in mice.
Microbiome diversity has been associated with improved outcomes after allogeneic stem-cell transplantation in patients with hematological cancers. Multimodal analysis of intestinal microbiome and metabolome data helped identify immunomodulatory microbial metabolites that were predictive of survival, transplant-related mortality and cancer relapse. These metabolites were products of short-chain-fatty-acid-synthesis pathways, and their associated genes were expressed by both bacterial species and bacteriophages.
Genomic features of de novo metastatic prostate cancer can clarify prognosis and direct therapy. Using multi-region profiling of synchronous primary and metastatic patient tissues, we reveal the complex evolutionary histories of this lethal disease and identify strategies to better capture the genomic features of dominant metastatic populations.
Cancer cells seed distant tissues and remain dormant before re-entering the cell cycle to form metastases. How tumor dormancy is maintained and how cells exit dormancy is poorly understood. A study shows that the lncRNA MALAT1 reactivates dormant cancer cells by upregulating serpin protease inhibitors in tumor cells to evade CD8+ T cells.
In vitro-transcribed RNA is a promising emerging class of therapeutic, but the poor specificity of cargo RNAs so far has limited their application in cancer immunotherapy. A new study reports the delivery of a synthetic circular RNA with inline cis-acting translational elements — encoding an engineered, mitochondrion-specific oncolytic protein — that shows both therapeutic and prophylactic potential against adenocarcinoma.
We developed a method for generating dendritic cell progenitors (DCPs) from hematopoietic stem and progenitor cells isolated from bone marrow or blood. When engineered to express IL-12 and FLT3L, these DCPs reprogram the tumor microenvironment and elicit anti-tumor immunity without the need for ex vivo antigen loading.
Twelve early-career investigators share their thoughts on the experiences they had starting their laboratories in 2023 and reflect on the opportunities they seized and the challenges they faced.
Transmissible cancer affects marine bivalve mollusks worldwide, but how genetic mechanisms influence cancer evolution and disease spread remains largely unexplored. Two new studies provide insights into the ancient origin of founder clones and the long-term tolerance of contagious cancer cells to extreme genome instability.
Chimeric antigen receptor T cells and T cell-redirecting bispecific antibody therapies are changing the landscape of myeloma therapy. Two studies investigate the genetic and epigenetic resistance mechanisms that lead to relapse in patients receiving T cell-engaging therapies targeting B cell maturation antigen (BCMA) and GPRC5D.
Certain cancers disrupt metabolism, leading to the wasting syndrome known as cachexia. How tumor-induced mediators of cachexia induce changes in end organs is unclear. A study implicates the endothelium as an amplifier of tumor signals in fat, in which NOTCH1 promotes adipose tissue remodeling via retinoic acid, IL-33 and IGFBP3.
The nervous system regulates cancer progression, and the importance of neuron–glioma communication in tumor growth is evident in glioblastoma. This tumor-promoting communication presents a potential therapeutic axis, a concept reinforced by a study that identifies a specific potassium channel complex as a therapeutic target.
The development of immunotherapies for acute myeloid leukemia (AML) has been limited by a lack of known tumor-specific targets. A study now shows the feasibility of developing highly sensitive and selective T cell-receptor-based therapies against an HLA-A*02:01-associated peptide derived from a recurrent mutation in a subset of patients with AML.
Jaffray and co-authors discuss progress in radiotherapy that has been driven by technological advances and ways to enable broad access to innovative radiation-based treatment modalities by aligning individualized therapy with global access needs.
We sought to develop a pharmacologically advanced inhibitor of the oncoprotein RET. Vepafestinib potently inhibited on-target mutants that confer resistance to approved RET inhibitors while exerting superior efficacy against intracranial disease due to enhanced penetration and retention in the brain.
Resected pancreatic cancer treated pre-operatively with chemotherapy is enriched for cells that co-express GATA6, KRT17 and CYP3A. Persistent expression of GATA6hi and KRT17hi is associated with poor survival after treatment with mFOLFIRINOX, but not gemcitabine. CYP3A-expressing drug detoxification pathways metabolize the prodrug irinotecan, a constituent of mFOLFIRINOX, leading to persistent drug tolerance.
Immunosuppressive myeloid cells, which are associated with resistance to anti-PD1 therapy in patients with glioblastoma, have high expression of KDM6B, an epigenetic enzyme. Deletion or inhibition of KDM6B reprograms the myeloid cells to an immunostimulatory phenotype and thereby overcomes resistance to anti-PD1 therapy in preclinical models of glioblastoma.
In this Review, Konstantinopoulos and Matulonis discuss recent clinical advances in the treatment of ovarian cancer and reflect on persisting challenges.
The recent design of mutation-selective KRAS inhibitors has led to US Food and Drug Administration approval of two inhibitors of KRAS(G12C), sotorasib and adagrasib. A study published in Nature reports the development of a first-in-class pan-KRAS-selective inhibitor. Here we comment on the current status of KRAS-targeting approaches.
The advantage of genomic monitoring over cytogenetics for clinical assessment of leukemia is illustrated by a case of pediatric acute lymphoblastic leukemia in which a lesion underlying lethal end-stage myeloid disease could be detected by whole-genome sequencing years before the risk manifested cytogenetically.
