Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer

Oncogenesis
Thomas C BeadnellRebecca E Schweppe

Abstract

Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway. Therefore, we examined the efficacy of the combination therapy across a panel of thyroid cancer cell lines representing common oncogenic drivers (BRAF, RAS, and PIK3CA). Interestingly, combined inhibition of Src and the MAPK pathway overcomes intrinsic dasatinib resistance in cell lines where both the MAPK and PI3K pathways are inhibited, which we show is likely due to the regulation of the PI3K pathway by Src in these responsive cells. Interest...Continue Reading

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Citations

Jan 29, 2020·Seminars in Cancer Biology·Nikita PozdeyevRebecca E Schweppe
Apr 3, 2021·Frontiers in Cell and Developmental Biology·Jingbin XuFasheng Li
Oct 2, 2021·Frontiers in Cell and Developmental Biology·Maxim L BychkovEkaterina N Lyukmanova

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Methods Mentioned

BETA
Assay
transfections
transfection

Software Mentioned

Image J
SANGER
R
Odyssey Image Studio
TreeView
R script
graphpad prism
glmnet
Elements
NIS

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