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Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1–HER3 signaling

Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.

Roberto Würth
Elisa Donato
Andreas Trumpp
ResearchOpen Access03 Jan 2025
Nature Cancer

Volume: 6, P: 67-85
TNF-α-producing macrophages determine subtype identity and prognosis via AP1 enhancer reprogramming in pancreatic cancer

Singh and colleagues show that PDAC phenotypic plasticity is regulated via AP1 enhancer remodeling and modulated by TNF-α⁺ macrophages and pharmacological inhibition of the BRD4–cJUN–CCL2–TNF-α axis restores favorable PDAC subtypes and prognosis.

Mengyu Tu
Lukas Klein
Shiv K. Singh
Research15 Nov 2021
Nature Cancer

Volume: 2, P: 1185-1203
Site-specific activation of the proton pump inhibitor rabeprazole by tetrathiolate zinc centres

Proton pump inhibitors (PPIs) are prodrugs that are activated by protonation in the highly acidic environment of the stomach lining. Now, coordination of PPIs to protein-bound zinc ions is revealed as another pathway to PPI activation. Acting as a Lewis acid, the zinc ion facilitates conjugation of the drug to zinc-coordinating cysteine residues.

Teresa Marker
Raphael R. Steimbach
Tobias P. Dick
ResearchOpen Access20 Feb 2025
Nature Chemistry

Volume: 17, P: 507-517
Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer

The mechanisms of intratumoral subtype heterogeneity in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, the authors analyse PDAC tumours and preclinical models using multi-omics and imaging; they demonstrate that AP1 dichotomy influences tumor plasticity, heterogeneity, and immune response, with potential therapeutic implications.

Lukas Klein
Mengyu Tu
Shiv K. Singh
ResearchOpen Access06 Jan 2025
Nature Communications

Volume: 16, P: 1-19
HAPLN1 potentiates peritoneal metastasis in pancreatic cancer

The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. Here the authors show that hyaluronan and proteoglycan link protein-1 (HAPLN1) promotes tumour cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers.

Lena Wiedmann
Francesca De Angelis Rigotti
Juan Rodriguez-Vita
ResearchOpen Access24 Apr 2023
Nature Communications

Volume: 14, P: 1-18
CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma

Expression of HNF1A and KRT81 stratifies pancreatic ductal adenocarcinoma tumors into different subtypes, and expression of cytochrome P450 3A5 mediates basal and/or drug-induced therapy resistance in each subtype.

Elisa M Noll
Christian Eisen
Martin R Sprick
Research08 Feb 2016
Nature Medicine

Volume: 22, P: 278-287
Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

Eduard Batlle and colleagues find that poor-outcome subgroups of colorectal cancer are driven by genes expressed in tumor-associated stromal cells. They show that TGF-β expression is a common feature of poor-prognosis subtypes and demonstrate the use of anti–TGF-β molecules in patient-derived tumoroids and xenografts.

Alexandre Calon
Enza Lonardo
Eduard Batlle
Research23 Feb 2015
Nature Genetics

Volume: 47, P: 320-329
MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Alborzinia et al. report that MYCN-amplified neuroblastoma undergoes ferroptosis in the absence of intracellular cysteine, suggesting a combination of cysteine depletion and concomitant GPX4 inactivation as a potential therapeutic approach.

Hamed Alborzinia
Andrés F. Flórez
Frank Westermann
ResearchOpen Access28 Apr 2022
Nature Cancer

Volume: 3, P: 471-485
Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts

Mireia Berdiel-Acer
Ana Maia
Stefan Wiemann
ResearchOpen Access10 Mar 2021
Oncogene

Volume: 40, P: 2651-2666

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