Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer
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...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15515 |
| _version_ | 1797457363534348288 |
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| author | Susanne Crocamo Renata Binato Everton Cruz dos Santos Bruno de Paula Eliana Abdelhay |
| author_facet | Susanne Crocamo Renata Binato Everton Cruz dos Santos Bruno de Paula Eliana Abdelhay |
| author_sort | Susanne Crocamo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:21:09Z |
| format | Article |
| id | doaj.art-e368febc77bb43629b5a59a2e8b94cc4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:21:09Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e368febc77bb43629b5a59a2e8b94cc42023-11-24T15:22:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241551510.3390/ijms232415515Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast CancerSusanne Crocamo0Renata Binato1Everton Cruz dos Santos2Bruno de Paula3Eliana Abdelhay4Núcleo de Pesquisa Clínica, Hospital de Câncer III, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro 20560-121, BrazilLaboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro 20230-130, BrazilLaboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro 20230-130, BrazilNúcleo de Pesquisa Clínica, Hospital de Câncer III, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro 20560-121, BrazilLaboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro 20230-130, BrazilBreast 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.https://www.mdpi.com/1422-0067/23/24/15515breast cancerHER2-positivedifferential expression geneszoledronic acid |
| spellingShingle | Susanne Crocamo Renata Binato Everton Cruz dos Santos Bruno de Paula Eliana Abdelhay Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer International Journal of Molecular Sciences breast cancer HER2-positive differential expression genes zoledronic acid |
| title | Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer |
| title_full | Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer |
| title_fullStr | Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer |
| title_full_unstemmed | Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer |
| title_short | Translational Results of Zo-NAnTax: A Phase II Trial of Neoadjuvant Zoledronic Acid in HER2-Positive Breast Cancer |
| title_sort | translational results of zo nantax a phase ii trial of neoadjuvant zoledronic acid in her2 positive breast cancer |
| topic | breast cancer HER2-positive differential expression genes zoledronic acid |
| url | https://www.mdpi.com/1422-0067/23/24/15515 |
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