Effects of neoadjuvant therapies on genetic regulation of targeted pathways in ER+ primary ductal breast carcinoma: A meta-analysis of microarray datasets.
Saudi Pharm J
; 29(7): 656-669, 2021 Jul.
Article
in En
| MEDLINE
| ID: mdl-34400859
ABSTRACT
Breast cancer arises as a result of multiple interactions between environmental and genetic factors. Conventionally, breast cancer is treated based on histopathological and clinical features. DNA technologies like the human genome microarray are now partially integrated into clinical practice and are used for developing new "personalized medicines" and "pharmacogenetics" for improving the efficiency and safety of cancer medications. We investigated the effects of four established therapies-for ER+ ductal breast cancer-on the differential gene expression. The therapies included single agent tamoxifen, two-agent docetaxel and capecitabine, or combined three-agents CAF (cyclophosphamide, doxorubicin, and fluorouracil) and CMF (cyclophosphamide, methotrexate, and fluorouracil). Genevestigator 8.1.0 was used to compare five datasets from patients with infiltrating ductal carcinoma, untreated or treated with selected drugs, to those from the healthy control. We identified 74 differentially expressed genes involved in three pathways, i.e., apoptosis (extrinsic and intrinsic), oxidative signaling, and PI3K/Akt signaling. The treatments affected the expression of apoptotic genes (TNFRSF10B [TRAIL], FAS, CASP3/6/7/8, PMAIP1 [NOXA], BNIP3L, BNIP3, BCL2A1, and BCL2), the oxidative stress-related genes (NOX4, XDH, MAOA, GSR, GPX3, and SOD3), and the PI3K/Akt pathway gene (ERBB2 [HER2]). Breast cancer treatments are complex with varying drug responses and efficacy among patients. This necessitates identifying novel biomarkers for predicting the drug response, using available data and new technologies. GSR, NOX4, CASP3, and ERBB2 are potential biomarkers for predicting the treatment response in primary ER+ ductal breast carcinoma.
BC, breast cancer; Bax, Bcl-2-associated X; Bcl2, B-cell lymphoma 2; CAF, cyclophosphamide, doxorubicin, and fluorouracil; CASP3; CMF, cyclophosphamide, methotrexate, and fluorouracil; Chemotherapy; DC, docetaxel and capecitabine; ER+ ductal carcinoma; ER, estrogen receptor; ERBB2 (HER2); FC, fold-change; FU, fluorouracil; GSR; H2O2, hydrogen peroxide; HER2, human epidermal growth factor 2; IGF-1, insulin-like growth factor-1; NOX4; OHâ, hydroxyl radical; PI3K/Akt, phosphatidylinositol 3-kinase/protein kinase B; PM, personalized medicine; PR, progesterone receptor; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ROS, reactive oxygen species; TGF-α/ß, transforming growth factor alpha/beta; TMX, tamoxifen; TS, thymidylate synthase
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
/
Systematic_reviews
Language:
En
Journal:
Saudi Pharm J
Year:
2021
Document type:
Article
Affiliation country:
Saudi Arabia