Emerging findings into molecular mechanism of brain metastasis

Abstract

Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

Brain Access of Monoclonal Antibodies as Imaged and Quantified by 89Zr-Antibody PET: Perspectives for Treatment of Brain Diseases

“…Here, an 18-fold higher uptake of trastuzumab was observed in brain metastasis as small as 0.7 mm, and previously undetected by MRI, than in normal brain tissue. This result is in line with growing evidence that brain metastasis could disrupt the BBB once the diameter exceeds 0.5 mm (9). The evidence that mAb delivery to brain metastasis is possible supports the use of trastuzumab therapy.…”

Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases

“…With improvements in primary tumor treatments, patient survival has increased, witnessing the development of metastases in 15–30% of BC patients [ 2 , 3 ]. Brain metastases (BM) limit both life expectancy and quality of life (QoL), being the main cause of death in BC patients, with an annual incidence of 8.3–14.3 per 100,000 individuals [ 4 , 5 ]. However, the mechanisms associated with BC brain metastases (BCBM) development are still unclear, rendering the unraveling of specific tumor molecular pathways necessary to develop innovative targeted therapeutics.…”

Silencing miR-202-3p increases MMP-1 and promotes a brain invasive phenotype in metastatic breast cancer cells

“…Brain metastasis is a complex multi-step process that includes epithelial-mesenchymal transition, tumor cells intravasation into the bloodstream or lymphatics, survival in the circulation, extravasation across the Blood-Brain Barrier (BBB), mesenchymal-epithelial transition and finally brain colonization [4][5][6][7][8]. A critical step in BM is the adhesion and transmigration of circulating metastatic cells through the blood-brain barrier (BBB), a process known as extravasation [9][10][11][12].…”