» Articles » PMID: 36555156

Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 Dec 23
PMID 36555156
Authors
Affiliations
Soon will be listed here.
Abstract

Breast cancer is a heterogeneous disease with distinct clinical and molecular characteristics. Scientific advances in molecular subtype differentiation support the understanding of cellular signaling, crosstalk, proliferation, survival, migration, and invasion mechanisms, allowing the development of new molecular drug targets. The breast cancer subtype with super expression and/or amplification of human growth factor receptor 2 (HER2) is clinically aggressive, but prognosis significantly shifted with the advent of anti-HER2 targeted therapy. Zoledronic-acid (ZOL) combined with a neoadjuvant Trastuzumab-containing chemotherapy regimen (Doxorubicin, Cyclophosphamide followed by Docetaxel, Trastuzumab) increased the pCR rate in a RH-positive/ HER2-positive subgroup, according to the phase II Zo-NAnTax trial. To verify genes that could be related to this response, a microarray assay was performed finding 164 differentially expressed genes. Silico analysis of these genes showed signaling pathways related to growth factors, apoptosis, invasion, and metabolism, as well as differentially expressed genes related to estrogen response. In addition, the RAC3 gene was found to interact with the MVD gene, a member of the mevalonate pathway. Taken together, these results indicate that RH-positive/ HER2-positive patients present gene alterations before treatment, and these could be related to the improvement of pCR.

Citing Articles

Survival outcomes of Zo-NAnTAx: a five-year analysis of zoledronic acid added to a neoadjuvant regimen for HER2-positive breast cancer.

de Paula B, Abdelhay E, de Sousa C, Crocamo S Ann Transl Med. 2024; 12(3):48.

PMID: 38911562 PMC: 11193563. DOI: 10.21037/atm-23-1880.


Two-Dimensional-PAGE Coupled with nLC-MS/MS-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in MCF7 Breast Cancer Cells Transfected for JTB Protein Silencing.

Jayathirtha M, Jayaweera T, Whitham D, Sullivan I, Petre B, Darie C Molecules. 2023; 28(22).

PMID: 38005222 PMC: 10673289. DOI: 10.3390/molecules28227501.


State-of-the-Art Molecular Oncology in Brazil.

Rodrigues T Int J Mol Sci. 2023; 24(11).

PMID: 37298404 PMC: 10253574. DOI: 10.3390/ijms24119452.

References
1.
Chalhoub N, Baker S . PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2008; 4:127-50. PMC: 2710138. DOI: 10.1146/annurev.pathol.4.110807.092311. View

2.
Guerra B, Recio C, Aranda-Tavio H, Guerra-Rodriguez M, Garcia-Castellano J, Fernandez-Perez L . The Mevalonate Pathway, a Metabolic Target in Cancer Therapy. Front Oncol. 2021; 11:626971. PMC: 7947625. DOI: 10.3389/fonc.2021.626971. View

3.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J . STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2014; 43(Database issue):D447-52. PMC: 4383874. DOI: 10.1093/nar/gku1003. View

4.
Rodriguez-Viciana P, Warne P, Vanhaesebroeck B, Waterfield M, Downward J . Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J. 1996; 15(10):2442-51. PMC: 450176. View

5.
Rexer B, Arteaga C . Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog. 2012; 17(1):1-16. PMC: 3394454. DOI: 10.1615/critrevoncog.v17.i1.20. View