Navigating the Blood-Brain Barrier: Challenges and Therapeutic Strategies in Breast Cancer Brain Metastases.

Breast cancer (BC) is the most common cancer in women, with metastatic BC being responsible for the highest number of deaths. A frequent site for BC metastasis is the brain. Brain metastasis derived from BC involves the cooperation of multiple genetic, epigenetic, angiogenic, and tumor-stroma interactions. Most of these interactions provide a unique opportunity for development of new therapeutic targets. Potentially targetable signaling pathways are Notch, Wnt, and the epidermal growth factor receptors signaling pathways, all of which are linked to driving BC brain metastasis (BCBM). However, a major challenge in treating brain metastasis remains the blood-brain barrier (BBB). This barrier restricts the access of unwanted molecules, cells, and targeted therapies to the brain parenchyma. Moreover, current therapies to treat brain metastases, such as stereotactic radiosurgery and whole-brain radiotherapy, have limited efficacy. Promising new drugs like phosphatase and kinase modulators, as well as BBB disruptors and immunotherapeutic strategies, have shown the potential to ease the disease in preclinical studies, but remain limited by multiple resistance mechanisms. This review summarizes some of the current understanding of the mechanisms involved in BC brain metastasis and highlights current challenges as well as opportunities in strategic designs of potentially successful future therapies.

Leaf and stem micromorphology of Byrsonima sericea DC. by light and scanning electron microscopy.

Micromorphological studies were carried out using multiple microscopic techniques on the leaves and stem bark of Byrsonima sericea DC. (Malpighiaceae), a species popularly known as "murici" and used medicinally, in order to identify both qualitative and quantitative features of leaf and stem anatomy and histochemistry as differential parameters to support both the quality control of its ethnodrugs and the taxonomy of the genus. The study was conducted using traditional techniques of plant anatomy, histochemical tests, and the stomatal index (SI). Byrsonima sericea has hypostomatic leaves, anomocytic stomata, and its epidermal walls are anticlinal and straight on the adaxial and curved on the abaxial faces. T-shaped trichomes were observed mainly on the abaxial surface. The leaf epidermis showed waxes syntopism on both surfaces, with the occurrence of different crystalloid forms on a single phylloplane. The mesophyll is dorsiventral, with 3-4 collateral vascular bundles. Phenolic compounds, starch, and proteins were identified in the petiole and stem. The SI was 14.5 ± 0.53% (p < .05), but did not showed significant variations. A set of characters were found to be distinctive for the studied species, however, constituting parameters that could be used to separate B. sericea from other species of the genus.