Tan DS
FOXA1 mutations reveal distinct chromatin profiles and influence therapeutic response in breast cancer
Mutations in the pioneer transcription factor FOXA1 are a hallmark of estrogen receptor-positive (ER+) breast cancers. Examining FOXA1 in ∼5,000 breast cancer patients identifies several hotspot mutations in the Wing2 region and a breast cancer-specific mutation SY242CS, located in the third β strand. Using a clinico-genomically curated cohort, together with breast cancer models, we find that FOXA1 mutations associate with a lower response to aromatase inhibitors.
ReadEffects of Single Nucleotide Polymorphisms on the Binding of Afatinib to EGFR: A Potential Patient Stratification Factor Revealed by Modeling Studies
The anticancer drug afatinib has been found to be more effective at inhibiting the oncogenic EGFR mutant exon 19 deletion (19del) over the oncogenic EGFR mutant L858R. The underlying mechanism has been hypothesized to result from differences in structural constraints introduced by the mutations and stabilizing interactions afforded by a buried water molecule in 19del (Kannan S. et al. Scientific Reports 2017, 7: 1540). The COSMIC cancer database is mined for EGFR sequences to discover that several mutations in the form of Single Nucleotide Polymorphisms (SNPs) line this hydration cavity.
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