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Purpose of Review: This review seeks to explore blood-based biomarkers with the potential for clinical implementation. Recent Findings: Emerging non-proteomic biomarkers hold promise for more accurate diagnostic and prognostic capabilities, especially in the subacute to chronic phase of TBI recovery. Further, there is a growing understanding of the overlap between TBI-related and Dementia-related blood biomarkers. Summary: Given the significant heterogeneity inherent in the clinical diagnosis of Traumatic Brain Injury (TBI), there has been an exponential increase in TBI-related biomarker research over the past two decades. While TBI-related biomarker assessments include both cerebrospinal fluid analysis and advanced neuroimaging modalities, blood-based biomarkers hold the most promise to be non-invasive biomarkers widely available to Brain Injury Medicine clinicians in diverse practice settings. In this article, we review the most relevant blood biomarkers for the field of Brain Injury Medicine, including both proteomic and non-proteomic blood biomarkers, biomarkers of cerebral microvascular injury, and biomarkers that overlap between TBI and Dementia.
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The majority of clinical deaths in patients with triple-negative breast cancer (TNBC) are due to chemoresistance and aggressive metastases, with high prevalence in younger women of African ethnicity. Although tumorigenic drivers are numerous and varied, the drivers of metastatic transition remain largely unknown. Here, we uncovered a molecular dependence of TNBC tumors on the TRIM37 network, which enables tumor cells to resist chemotherapeutic as well as metastatic stress. TRIM37-directed histone H2A monoubiquitination enforces changes in DNA repair that rendered TP53-mutant TNBC cells resistant to chemotherapy. Chemotherapeutic drugs triggered a positive feedback loop via ATM/E2F1/STAT signaling, amplifying the TRIM37 network in chemoresistant cancer cells. High expression of TRIM37 induced transcriptomic changes characteristic of a metastatic phenotype, and inhibition of TRIM37 substantially reduced the in vivo propensity of TNBC cells. Selective delivery of TRIM37-specific antisense oligonucleotides using antifolate receptor 1-conjugated nanoparticles in combination with chemotherapy suppressed lung metastasis in spontaneous metastatic murine models. Collectively, these findings establish TRIM37 as a clinically relevant target with opportunities for therapeutic intervention. SIGNIFICANCE: TRIM37 drives aggressive TNBC biology by promoting resistance to chemotherapy and inducing a prometastatic transcriptional program; inhibition of TRIM37 increases chemotherapy efficacy and reduces metastasis risk in patients with TNBC.