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May 31 2025
4Breast cancer remains one of the most prevalent cancers among women globally. Approximately 15–20% of these cases are characterized by an overexpression of the HER2 protein, a condition that often leads to aggressive tumor growth and a higher likelihood of recurrence. Trastuzumab, a monoclonal antibody, has been a cornerstone in treating HER2-positive breast cancer. However, resistance to this therapy develops in a significant number of patients, with up to 70% experiencing resistance within a year.PubMed+1ResearchGate+1
Recent research conducted by Xiaohong Fang and her team at the Chinese Academy of Sciences has shed light on a potential contributor to this resistance: the bacterium Pseudomonas aeruginosa. This microorganism, commonly found within breast tumors, produces a signaling molecule known as N-(3-oxo-dodecanoyl) homoserine lactone (3OC12-HSL or 3oc). While 3oc is known to induce apoptosis in immune cells, its effect on tumor cells was previously unclear.
In their study, Fang's team treated various breast cancer cell lines with 3oc and observed an increase in resistance to trastuzumab across all tested lines, including those previously sensitive to the drug. Notably, 3oc did not affect the viability of the cancer cells directly but appeared to activate specific signaling pathways within them.
Further analysis revealed that 3oc activates the TGF-β signaling pathway, which in turn stimulates the HER2 pathway downstream, effectively bypassing the inhibitory action of trastuzumab. This activation was confirmed by observing the phosphorylation of signal transducers in the TGF-β pathway. When the cells were treated with a TGF-β inhibitor, this effect was nullified, indicating a direct link between 3oc-induced TGF-β activation and trastuzumab resistance.
To validate their findings in a clinical context, the researchers examined breast tumor samples from patients. Using quantitative PCR and fluorescence in situ hybridization, they detected P. aeruginosa in 7 out of 34 tumor samples. Moreover, 3oc was identified in 8 out of 24 tumors through liquid chromatography-mass spectrometry. Importantly, tumors from patients who did not respond fully to trastuzumab treatment were more likely to contain P. aeruginosa, suggesting a correlation between the presence of this bacterium and therapeutic resistance.
These findings underscore the potential role of intratumoral bacteria in influencing the efficacy of cancer therapies. As Melanie Rutkowski, an immunologist at the University of Virginia, noted, this research opens new avenues for understanding resistance mechanisms and highlights the microbiome's potential impact on treatment outcomes.
The study emphasizes the need for further exploration into how microbial communities within tumors can affect cancer progression and response to therapy. Understanding these interactions could lead to novel strategies to overcome resistance and improve patient outcomes in HER2-positive breast cancer.
Source:https://www.the-scientist.com/a-bacterial-signaling-molecule-lends-tumors-drug-resistance-73045
This is non-financial/medical advice and made using AI so could be wrong.
