Abstract
Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unresolved problem. Understanding these events will reveal disease-based targets and offer effective strategies to treat brain metastases. Effective therapeutic strategies based upon the biology of brain metastases represent an urgent, unmet need with immediate potential for clinical impact. Studies have demonstrated the ability of miRNAs to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on miRNA profiles. Interestingly, manipulation of miRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy and individually directed personalized anti-cancer therapy, using miRNA in the treatment of metastatic brain tumors may prove very useful and improve patient outcome. In this review, we focus on the potential of miRNAs as diagnostic and therapeutic targets for the treatment of metastatic brain lesions.
Highlights
The treatment of metastatic brain tumors remains a daunting challenge
Brain metastases continue to increase as a result of an aging population, the advent of targeted therapies that have increased the survival of patients with primary tumors and superior methods that allow earlier cancer detection [3]
MiRNA-768-3p was down-regulated in tumor cells when co-cultured with astrocytes and this was validated in human brain metastatic tissues from lung cancer, breast cancer and melanoma when compared to match-paired primary tumor from the same patient
Summary
The treatment of metastatic brain tumors remains a daunting challenge. Metastatic brain lesions are the most frequently occurring intracranial tumors in adults with >170,000 patients diagnosed annually in the US—ten times the incidence of primary brain tumors [1,2]. Current models of brain metastasis, such as transgenic and subcutaneous tumors implanted into immunodeficient mice, do not adequately represent the clinical scenario These models do not reflect the precise molecular steps involved in metastasis nor the response to therapeutic agents. Was developed to transplant histologically-intact human cancer cells or tissue, taken directly from patients, into the corresponding organ of immunodeficient mice These unique SOI models have been successfully used for innovative drug discovery and mechanistic studies and serve as a bridge to link pre-clinical studies with clinical research and drug development. Inhibiting p-glycoprotein, has not proved successful in reversing chemoresistance These studies indicate that unidentified mechanisms underlie the pro-survival effect of the brain microenvironment which has led to the search for genetic regulators. The leakage of contrast material (gadolinium) into and around the tumor rules out the blood–brain barrier as the sole mechanism for drug resistance
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