Biological mechanisms of resistance to trastuzumab and ways to overcome them: Mod-ern problems of clinical oncology

Regulatory Mechanisms in Biosystems, Journal Year: 2024, Volume and Issue: 15(2), P. 345 - 352

Published: May 11, 2024

In 2022, 2.3 million new cases of breast cancer were registered in the world, which accounted for 11.6% total number malignant neoplasms. Depending on tumor's molecular profile, prognosis patients can be different. One most aggressive types is HER2-positive cancer. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, used to treat such tumors. Congenital or acquired resistance trastuzumab one essential problems clinical oncology. Our study aimed investigate mechanisms and ways overcome them. This drug influences several directions oncogenesis at same time. The fundamental action are inhibition HER2 ectodomain shedding, angiogenesis, degradation protein its internalization, DNA repair, influence phosphatidylinositol 3-kinase pathway, cell cycle antibody-dependent cellular cytotoxicity. biological based vascular mimicry hypoxia, appearance stem cells, activation alternative signaling pathways, metabolic changes, variants changes processes immune regulation, heterogeneity expression stability protein. modern oncology, as an original product antibody-drug conjugates. Trastuzumab emtansine deruxtecan approved treatment with cancer, including those low expression. literature review identified implementation targeted drugs combination way personalized treatment. It significantly improve survival

Language: Английский

Investigating the Correlation Between Long-Term Response in Patients with Metastatic HER2+ Breast Cancer and the Activity of Regulatory T Cells: A Retrospective Study

Breast Cancer Targets and Therapy, Journal Year: 2024, Volume and Issue: Volume 16, P. 645 - 655

Published: Sept. 1, 2024

Trastuzumab is commonly utilized in the management of metastatic HER2-positive breast cancer. Our main goal was to examine clinical outcomes and immune markers patients who received trastuzumab chemotherapy treatment.

Language: Английский

Association of Granulocyte Colony-Stimulating Factor Treatment with Risk of Brain Metastasis in Advanced Stage Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10756 - 10756

Published: Oct. 6, 2024

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment chemotherapy-induced neutropenia febrile because risks associated with certain types cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined association between GCSF incidence brain metastasis (BM), as well BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at time diagnosis who received least one course systematic chemotherapy target therapy a tertiary teaching hospital 1 January 2014 31 December 2022. effect on was assessed other confounding factors in Cox regression analyses. In this cohort, had significantly higher than those did (34.9% vs. 13.8%, p = 0.011). Univariate analysis showed that use, menopause status, hormone treatment, HER2 cumulative dosage, dosage density, were independent risk BMFS (p < 0.05). users (adjusted HR: 2.538; 95% CI: 1.127–5.716, 0.025) nonusers. (RR: 1.84, 1.21, 2.80) but 0.59, 0.41–0.84, Interaction p-value dose density GCSF, compared do trend 0.01). These preliminary results suggest have initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our results.

Language: Английский