Mechanisms Supporting the Use of Beta-Blockers for the Management of Breast Cancer Bone Metastasis

Abstract

The skeleton is heavily innervated by sympathetic nerves and represents a common site for breast cancer metastases, the latter being the main cause of morbidity and mortality in breast cancer patients. Progression and recurrence of breast cancer, as well as decreased overall survival in breast cancer patients, are associated with chronic stress, a condition known to stimulate sympathetic nerve outflow. Preclinical studies have demonstrated that sympathetic stimulation of β-adrenergic receptors in osteoblasts increases bone vascular density, adhesion of metastatic cancer cells to blood vessels, and their colonization of the bone microenvironment, whereas β-blockade prevented these events in mice with high endogenous sympathetic activity. These findings in preclinical models, along with clinical data from breast cancer patients receiving β-blockers, support the pathophysiological role of excess sympathetic nervous system activity in the formation of bone metastases, and the potential of commonly used, safe, and low-cost β-blockers as adjuvant therapy to improve the prognosis of bone metastases.

Identification of therapeutically potential targets and their ligands for the treatment of OSCC

“…Beta-blockers have shown good antineoplastic activity in various cancer cell lines. They are also reported to increase the effect of anticancer chemotherapy ( 91 , 92 ). Therefore, labetalol, having a mix of alpha- and beta-blocker activities, can be a potential candidate for the treatment of OSCC.…”

Enhancer RNA SLIT2 Inhibits Bone Metastasis of Breast Cancer Through Regulating P38 MAPK/c-Fos Signaling Pathway

“…When BRCA spreads beyond the breast, one of the most common places is the bones (25). Bone metastases occur in roughly 70% of women and are often the first symptom that the BRCA has relapsed, and finding and treating bone metastases early on can be critical in preventing problems later (26). Thus, this study aimed to analyze transcriptomic profiles of bone metastatic tumor to identify prognostic biomarkers to control metastasis.…”

Adding recombinant AAVs to the cancer therapeutics mix

“…Regardless of tumor type, once metastasis occurs and the primary tumor spreads to distant secondary sites, the 5-year survival rate of the patient dramatically decreases, emphasizing the need for early effective treatments and metastasis-specific therapies that prolong survival. 1 , 4 , 10 , 22 , 130 , 131 , 132 , 133 , 134 , 135 The cells of a tumor that metastasize to a secondary organ express a genetic profile that is different from the primary tumor, a characteristic of tumor heterogeneity that in some ways makes metastatic cancer its own distinct disease. 130 , 132 , 134 , 136 For example, several groups report specific secretome and genetic profiles of metastatic clones of cancer cell lines compared with the parental line, a biological trait that can be exploited by the engineering versatility of AAVs to specifically and effectively target subgroups of cancers located in either a primary or secondary site.…”

“…It is well-documented that non-cancerous cells, extracellular matrices, and physical properties of various organs and regions of the body facilitate tumor development and metastasis. 21 , 130 , 131 , 133 , 135 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 Because of these data, several conventional cancer therapeutics indeed have been designed to block signaling of and interactions between stromal cells such as cancer-associated fibroblasts, vasculature, and pro-tumor immune cells, and tumor cells with varying successes. 22 , 152 , 153 , 154 , 155 , 156 , 157 In the context of gene therapy, rAAVs are also being designed to target these types of tumor-supporting cells.…”