scholarly journals MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Weihua Jiang ◽  
Xiao-Liang Xing ◽  
Chenguang Zhang ◽  
Lina Yi ◽  
Wenting Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Fatty Acid Synthase ◽  
Triple Negative ◽  
Predictive Ability ◽  
Pathological Characteristic ◽  
Positive Expression ◽  
Combined Use ◽  
Mesenchymal Epithelial Transition Factor ◽  
Mesenchymal Epithelial Transition

BackgroundTo know the expression of Mesenchymal–Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.Methodswe used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.Results130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.ConclusionsOur results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC.

scholarly journals CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Hong Luo ◽  
Zhicheng Zhou ◽  
Shan Huang ◽  
Mengru Ma ◽  
Manyu Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Triple Negative Breast Cancer ◽  
Fatty Acid Synthase ◽  
Triple Negative ◽  
Trichostatin A ◽  
Affinity Purification ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Breast Cancers

AbstractFailures to treat triple-negative breast cancer (TNBC) are mainly due to chemoresistance or radioresistance. We and others previously discovered that zinc finger E-box-binding homeobox 1 (ZEB1) is a massive driver causing these resistance. However, how to dynamically modulate the intrinsic expression of ZEB1 during cell cycle progression is elusive. Here integrated affinity purification combined with mass spectrometry and TCGA analysis identify a cell cycle-related E3 ubiquitin ligase, checkpoint with forkhead and ring finger domains (CHFR), as a key negative regulator of ZEB1 in TNBC. Functional studies reveal that CHFR associates with and decreases ZEB1 expression in a ubiquitinating-dependent manner and that CHFR represses fatty acid synthase (FASN) expression through ZEB1, leading to significant cell death of TNBC under chemotherapy. Intriguingly, a small-molecule inhibitor of HDAC under clinical trial, Trichostatin A (TSA), increases the expression of CHFR independent of histone acetylation, thereby destabilizes ZEB1 and sensitizes the resistant TNBC cells to conventional chemotherapy. In patients with basal-like breast cancers, CHFR levels significantly correlates with survival. These findings suggest the therapeutic potential for targeting CHFR-ZEB1 signaling in resistant malignant breast cancers.

scholarly journals Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Na Young Jang ◽  
Dan Hyo Kim ◽  
Bong Jun Cho ◽  
Eun Jung Choi ◽  
Jong-Soo Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Combined Use

Inhibiting fatty acid synthase in operable triple negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 584-584
Author(s):  
Sagar D. Sardesai ◽  
Alexandra Thomas ◽  
Christopher Gallagher ◽  
Filipa Lynce ◽  
Yvonne Lynn Ottaviano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Triple Negative Breast Cancer ◽  
Fatty Acid Synthase ◽  
Triple Negative ◽  
Population Change ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Breast Cancer Cell Lines ◽  
High Dose

584 Background: Fatty acid synthase (FASN) is overexpressed in 70% of newly diagnosed triple negative breast cancer (TNBC) and is associated with poor prognosis. In vitro, FASN overexpression induces drug resistance to DNA damaging agents. Proton pump inhibitors (PPI) selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells. We report the results of a single arm phase II study of high dose omeprazole (OMP) in combination with anthracycline- taxane (AC-T) based neoadjuvant chemotherapy. Methods: Patients (pts) with operable TNBC independent of baseline FASN expression; and no prior PPI use within 12 months were enrolled. Pts began OMP 80 mg PO BID for 4-7 days prior to AC-T; carboplatin was allowed per physician discretion. OMP was continued until surgery. Paired biopsy samples were obtained before and after OMP monotherapy. The primary endpoint was pathologic complete response (pCR), defined as no residual invasive disease in breast or axilla, in pts with baseline FASN expression (FASN+) assessed using immunohistochemistry. Relevant secondary endpoints included pCR in the intent to treat population, change in FASN expression, enzyme activity and downstream target gene expression after OMP monotherapy; safety and limited OMP pharmacokinetics. We targeted a pCR rate of 60% in FASN+ pts (null pCR ~ 40%) with 80% power and alpha of 0.10. Results: A total of 42 pts were recruited from 5 US sites. Median age was 51y (28-72). Most pts had >cT2 (33, 79%) and ≥N1 (22, 52%) disease. 14 (33%) were African American. FASN expression prior to AC-T was identified in 28 (85%) samples available for analysis. The pCR rate was 71.4% (95% CI 51.3 to 86.8) in FASN+ pts and 71.8 %( 95% CI 55.1 to 85.0) in all enrolled pts. Fifteen pts (36%) received carboplatin with AC-T; pCR in this subset was 73%. Peak OMP concentration was significantly higher than IC50 observed during preclinical testing; FASN positivity significantly decreased with OMP monotherapy from 0.53(SD 0.25) at baseline to 0.38(SD 0.30; p = 0.02). OMP was well tolerated with no known grade (G) 3 or 4 toxicities. Chemotherapy toxicity was similar to prior studies using AC-T with G3 or 4 neutropenia (19%), febrile neutropenia (7%) and peripheral neuropathy (7%) being the most common. Conclusions: Consistent with previous studies, FASN is frequently expressed in early stage TNBC. OMP can be safely administered in doses that inhibit FASN. The addition of high dose OMP to neoadjuvant AC-T yields a promising pCR rate without adding toxicity. Funded by the Breast Cancer Research Foundation. Clinical trial information: NCT02595372 .

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