Association of Low Tumor Endothelial Cell pY397–Focal Adhesion Kinase Expression With Survival in Patients With Neoadjuvant-Treated Locally Advanced Breast Cancer

Abstract

Key Points Question Are phosphorylated–focal adhesion kinase (pY397-FAK) expression levels in endothelial or tumor cells and tumor blood vessel density associated with response to chemotherapy and relapse-free survival after neoadjuvant chemotherapy in patients with locally advanced breast cancer? Findings In this prognostic study of 82 women with stage IIA to IIIC locally advanced breast cancer, low endothelial cell pY397-FAK expression levels in prechemotherapy core biopsies were associated with sensitivity to neoadjuvant chemotherapy and improved 5-year relapse-free survival. Combined analysis of high endothelial cell pY397-FAK, high tumor cell pY397-FAK, and high blood vessel density appeared to identify a high-risk population. Meaning The findings of this study suggest that endothelial cell pY397-FAK levels could be used as a clinical tool for indicating response to neoadjuvant chemotherapy.

Functional and clinical characteristics of focal adhesion kinases in cancer progression

“…Multiple methods, including western blotting (WB), quantitative real-time polymerase chain reaction (qPCR), and immunohistochemistry (IHC), have shown increased FAK expression or enhanced activity in many human cancers, including lung ( Zhou et al, 2018 ; Aboubakar Nana et al, 2019b ), head and neck ( Zhang and Sun, 2020 ), oral cavity ( Kato et al, 2020 ), thyroid ( Ignjatović et al, 2021 ), breast ( Roy-Luzarraga et al, 2020 ), ovarian ( Li et al, 2015 ), prostate ( Goto et al, 2020 ), colon ( Murata et al, 2008 ), liver ( Francalanci et al, 2020 ), stomach ( Luo et al, 2020 ), pancreatic ( Furuyama et al, 2006 ), kidney ( Béraud et al, 2015 ), skin ( Najjar et al, 2020 ), and bone ( Thanapprapasr et al, 2017 ; Gu and Zhou, 2018 ) cancer. In addition, an increased expression or activity of FAK has been reported in various cancer cell lines ( Aboubakar Nana et al, 2019c ).…”

Focal adhesion kinase: from biological functions to therapeutic strategies

“…In addition, inhibiting endothelial FAK enhances the response of B16 and CMT19T mouse tumors to adriamycin or radiotherapy by suppressing NF-κB activation and cytokine production, thereby improving the effectiveness of DNA damage therapy [ 158 ]. Furthermore, elevated EC-PY397-FAK expression levels are strongly correlated with advanced clinical parameters of breast cancer and poor treatment response and independently predict unfavorable five-year recurrence-free survival, which highlights the need to assess the role of FAK inhibitors in optimizing treatments and improve the response to various strategies [ 159 ].…”