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A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
(NATURE PUBLISHING GROUP, 2020-06-26)
Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ...
PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.
(NATURE PORTFOLIO, 2022-02-01)
The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase ...
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
(OXFORD UNIV PRESS INC, 2022-06-01)
We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an ...
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
(NATURE PORTFOLIO, 2018-01-23)
There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples ...
Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.
(BMC, 2022-06-10)
BACKGROUND: Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new ...
Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives.
(HINDAWI LTD, 2017-01-01)
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3-5% of them survive for ...
DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer.
(BMC, 2016-09-15)
BACKGROUND: The APOBEC3 family of cytidine deaminases mutate the cancer genome in a range of cancer types. Although many studies have documented the downstream effects of APOBEC3 activity through next-generation sequencing, ...
Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma.
(IMPACT JOURNALS LLC, 2016-10-04)
Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/ amplified in pediatric HGG, but the significance of this ...
Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer.
(AMER SOC CLINICAL INVESTIGATION INC, 2018-10-01)
BACKGROUND: Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection. METHODS: Defective mismatch repair (dMMR) status was determined by either loss ...
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-03-07)
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...