Summary of the triple negative manuscript JECC-S-24-01481-1

A breast cancer subtype, Tripe-Negative Breast Cancer (TNBC), is a highly heterogeneous disease defined by the absence of estrogen receptor (ER), progesterone receptor (PR) expression and lack of Her2 overexpression. Among breast cancers, TNBC exhibits a higher proliferation rate, higher incidence of metastases to the brain, liver, and lungs. The lack of hormon receptors (ER and PR) and lack of Her2 overexpression prevent the use of usual targeted treatments, leaving chemotherapy as the only systemic therapeutic alternative. Trastuzumab is currently use as treatment for patients with Her2 overexpression. In the current manuscript we have investigated the effects of trastuzumab linked to micelles on TNBC cell lines by using various cell culture models and Balb/c-4T1 animal model.  We found that trastuzumab exhibits anti-tumoral properties on TNBC cell lines only when linked to pH-sensitive micelles. In addition, the data demonstrate that functionalized micelles impair the metastasis by reducing the number and sizes of metastases. Even more, the tested functionalized micelles impair formation of cancer stem cells, responsible for cancer progression and recurrence. The in vitro biological effects we have seen in human and murine TNBC cell lines are not observed in the widely used normal human breast cell line MCF-10A. Taken together, these results indicate that functionalization of micelles by linking trastuzumab may open the way of treating the TNBC and Her2 negative patients with theses functionalized nanocarriers. Due to the usual manuscript length restrictions, this manuscript does not contain the extended details regarding the preparation and characterization of micelles, which represent the core of another manuscript.

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