-
3 weeks ago | 
nature.com | Zheqi Li |Xintao Qiu |Marco Seehawer |Maeve McFadden |Eva Papachristou |Natalie Kingston | +17 more
AbstractBasal breast cancer is a subtype with a poor prognosis in need of more effective therapeutic approaches. Here we describe a unique role for the KDM4C histone lysine demethylase in KDM4C-amplified basal breast cancers, where KDM4C inhibition reshapes chromatin and transcriptomic landscapes without substantial alterations of its canonical substrates, trimethylated histone H3 lysine 9 (H3K9me3) and lysine 36 (H3K36me3).
-
Nov 12, 2024 | 
nature.com | Alvaro Curiel-Garcia |Margo I Orlen |Clint A. Stalnecker |Julien Dilly |Marie C. Hasselluhn |Stephanie Chang | +16 more
Correction to: Nature https://doi.org/10.1038/s41586-024-07379-z Published online 8 April 2024In the version of the article initially published, in the Data availability section, the GEO accession number was incorrect and has now been amended to GSE252002 in the HTML and PDF version of the article.
-
Apr 25, 2024 | 
nature.com | Matthew Rees |Melissa Ronan |Jennifer Roth |Yingzhe Wang |Brent A. Orr |Brian J. Abraham | +3 more
AbstractChemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD).
-
Apr 8, 2024 | 
nature.com | Grace Goodhart |Julien Dilly |Nicole Nasholm |Tamar Ziv |Jennifer Roth |Matthew Rees | +9 more
AbstractRAS oncogenes (collectively NRAS, HRAS and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRAS(G12C) oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small cell lung cancer2,3.
-
Apr 8, 2024 | 
nature.com | Alvaro Curiel-Garcia |Margo I Orlen |Clint A. Stalnecker |Julien Dilly |Marie C. Hasselluhn |Stephanie Chang | +16 more
AbstractBroad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants (RAS(ON) multi-selective)3.
-
Feb 23, 2024 | 
nature.com | Liang Chang |Nancy jung |diego rodriguez |Diego Rodríguez |Tian-Yu Song |Matthew Rees | +3 more
Correction to: Nature Genetics https://doi.org/10.1038/s41588-023-01515-7, published online 25 September 2023. In the version of the article initially published, Fig. 5f was originally divided into two panels, f and g, but these have now been combined to reflect the fact that they are from the same experiment. Panel g contained a duplicated NFT1 row from panel f, followed by the CSNK1A1 shRNA row, which now appears in panel f. Fig. 5 has been amended in the HTML and PDF versions of the article.
-
Dec 27, 2023 | 
nature.com | Marc Payton |Andrew Boghossian |Matthew Rees |Melissa Ronan |Jennifer Roth
AbstractChromosomal instability (CIN) is a hallmark of cancer, caused by persistent errors in chromosome segregation during mitosis. Aggressive cancers like high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) have a high frequency of CIN and TP53 mutations. Here, we show that inhibitors of the KIF18A motor protein activate the mitotic checkpoint and selectively kill chromosomally unstable cancer cells.
-
Oct 26, 2023 | 
nature.com | Christoph Gorgulla |Sara Marchese |Sergio Valente |Thibault Viennet |Melissa Ronan |Matthew Rees | +5 more
AbstractNADPH oxidases (NOXs) are transmembrane enzymes that are devoted to the production of reactive oxygen species (ROS). In cancers, dysregulation of NOX enzymes affects ROS production, leading to redox unbalance and tumor progression. Consequently, NOXs are a drug target for cancer therapeutics, although current therapies have off-target effects: there is a need for isoenzyme-selective inhibitors.
-
Oct 4, 2023 | 
nature.com | Christina Baumgartner |Arvin Iracheta-Vellve |Kira E. Olander |Omar Ávila |Audrey J. Muscato |James C. Patti | +13 more
AbstractImmune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3,4,5,6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.
-
Sep 25, 2023 | 
nature.com | Liang Chang |Nancy jung |diego rodriguez |Diego Rodríguez |Tian-Yu Song |Matthew Rees | +3 more
AbstractThe paradigm of cancer-targeted therapies has focused largely on inhibition of critical pathways in cancer. Conversely, conditional activation of signaling pathways as a new source of selective cancer vulnerabilities has not been deeply characterized. In this study, we sought to systematically identify context-specific gene-activation-induced lethalities in cancer.
