2020
DOI: 10.1101/2020.07.09.195974
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Transcriptomically-inferred PI3K activity and stemness show a counterintuitive correlation withPIK3CAgenotype in breast cancer

Abstract: ABSTRACTThe development of reliable, prognostically informative molecular tests to direct targeted cancer therapy is a major challenge. In 2019, the PI3Kα inhibitor alpelisib was approved for the treatment of advanced breast cancer, in combination with the oestrogen receptor degrader fulvestrant, with some evidence for improved therapeutic response in patients classified as having tumours which were positive for mutation in PIK3CA, the gene encoding P… Show more

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Cited by 2 publications
(1 citation statement)
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“…BYL719 (alpelisib; Novartis), the PI3Kα-selective inhibitor used in our cellular studies, was recently approved for use in combination with anti-oestrogen therapy in oestrogen receptor-positive breast cancers ( André et al, 2019 ). In a separate study focusing on human breast cancer, we have described the use of computational analyses to demonstrate a strong positive relationship between a transcriptomically derived PI3K activity score, stemness gene expression and tumour grade in breast cancer ( Madsen et al, 2020 preprint). Previous reports have suggested a role for NODAL in driving breast cancer stemness and aggressive disease ( Bar-Eli, 2012 ; Margaryan et al, 2019 ), with potential links to mTORC1 activation ( Katsuno et al, 2019 ; Jewer et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
“…BYL719 (alpelisib; Novartis), the PI3Kα-selective inhibitor used in our cellular studies, was recently approved for use in combination with anti-oestrogen therapy in oestrogen receptor-positive breast cancers ( André et al, 2019 ). In a separate study focusing on human breast cancer, we have described the use of computational analyses to demonstrate a strong positive relationship between a transcriptomically derived PI3K activity score, stemness gene expression and tumour grade in breast cancer ( Madsen et al, 2020 preprint). Previous reports have suggested a role for NODAL in driving breast cancer stemness and aggressive disease ( Bar-Eli, 2012 ; Margaryan et al, 2019 ), with potential links to mTORC1 activation ( Katsuno et al, 2019 ; Jewer et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%