Regulation mechanism and biomechanics effects of HER2 overexpression-related signalling pathway and targeted therapeutic strategy in breast cancer
Abstract
HER2 overexpression is an important pathogenic factor in breast cancer, affecting tumour proliferation and metastasis. In addition to molecular factors, the mechanical microenvironment within the tumour, including interstitial fluid pressure and shear stress, has been emerging as a significant regulator of cancer cell behavior. These mechanical forces can potentially interact with HER2-related signaling pathways, influencing the progression of breast cancer. The study investigated the regulatory mechanisms of HER2 overexpression-related signalling pathways and their targeted therapeutic effects in HER2-positive breast cancer patients receiving neoadjuvant therapy. Gene amplification and protein overexpression of HER2 were assessed by biomarker analysis, clinical data evaluation and survival analysis according to HER2 expression. The progression-free survival and overall survival of the experimental group (HER2-targeted therapy group and combination therapy group) were significantly better than that of the control group (chemotherapy-only group) after treatment, with PFS of 18.4 and 21.2 months, respectively, compared with 12.6 months in the control group (P < 0.05). Biomechanically, this indicates a more favorable response in terms of the mechanical stability and growth inhibition of tumors in the experimental groups. The level of HER2 receptor was significantly decreased in the experimental group after treatment (P < 0.01), and the cell-cycle analysis showed that the targeted cell cycle was stalled at G1 phase in the treatment group. This effectively inhibited the proliferation of breast cancer cells, potentially altering their mechanical interactions with the surrounding tissue. The activation level of HER2-related signalling pathway was significantly reduced in the targeted therapy group, and the expression of HER2 protein within the treatment group also showed a downward trend. These molecular alterations are likely to impact the biomechanical properties of the cells, such as their stiffness and motility. HER2-targeted therapy significantly improved the treatment effect of HER2-positive breast cancer patients by regulating the signalling pathways such as PI3K/Akt, RAS/MAPK and JAK-STAT. In the context of biomechanics, these pathways are involved in regulating cell-matrix interactions, cell-cell adhesion, and intracellular force generation. The combination therapy is superior to HER2-targeted therapy alone in improving the tumour shrinkage rate, which is of potential clinical value and provides a more precise therapeutic strategy and biomechanics basis for neoadjuvant treatment of HER2-positive breast cancer.
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