Circulating Biomarkers in Migraine: New Opportunities for Precision Medicine.

BACKGROUND: Migraine is the most common neurological disorder and the second most disabling human condition, whose pathogenesis is favored by a combination of genetic, epigenetic, and environmental factors. In recent years, several efforts have been made to identify reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a specific treatment. OBJECTIVE: To review the current evidence on the potential biological markers associated with migraine. METHODS: A structured search of peer-reviewed research literature was performed by searching major publications databases up to December 2017. RESULTS: Several circulating biomarkers have been proposed as diagnostic or therapeutic tools in migraine, mostly related to migraine's inflammatory pathophysiological aspects. Nonetheless, their detection is still a challenge for the scientific community, reflecting, at least in part, disease complexity and clinical diagnostic limitations. At the present time, calcitonin generelated peptide (CGRP) represents probably the most promising candidate as a diagnostic and/or therapeutic biomarker, as its plasma levels are elevated during migraine attack and decrease during successful treatment. Other molecules (including some neuropeptides, cytokines, adipokines, or vascular activation markers) despite promising, do not possess the sufficient prerequisites to be considered as migraine biomarkers. CONCLUSION: The characterization of migraine-specific biomarkers would be fundamental in a perspective of precision medicine, enabling risk assessment and tailored treatments. However, speculating on the clinical validity of migraine biomarkers may be premature and controlled clinical trials are presently needed to investigate both the diagnostic and therapeutic value of these biomarkers in migraine.

Anti-Angiogenic Drugs, Vascular Toxicity and Thromboembolism in Solid Cancer.

BACKGROUND: Neo-angiogenesis, a key step in cancer progression, is a highly regulated process, in which Vascular Endothelial Growth Factor (VEGF) plays a fundamental role, thus representing the most suitable anti-angiogenic target. In the last year, a number of anti-VEGF drugs have been developed and approved for therapeutic use, especially in combination with standard chemotherapy. VEGF, however, is not only crucial for physiological and pathological angiogenesis, but also for the maintenance of vascular homeostasis, at a point that its pharmacological blockade may lead to endothelial dysfunction and adverse vascular effects, such as venous thromboembolism. The picture is further complicated by the understanding that the amount of VEGF production is influenced by genetic factors, with environmental ones accounting only for 20-30% of its variations. This has recently prompted the design of various pharmacogenetic studies to investigate the role of VEGF polymorphisms in determining the pharmacological response and safety profile of various anti-angiogenic drugs, suggesting that the analysis of VEGF genetic variants in cancer patients may further help personalize anti-angiogenic pharmacological strategies. CONCLUSION: In this review, we initially focused on the biological mechanisms involved in vascular maintenance and angiogenesis. Then, discussed the efficacy and toxicity profile of some of the antiangiogenic drugs most commonly used in the treatment of solid cancer, with a particular focus on the thromboembolic complications of anti-angiogenic treatments in cancer patients. Finally, the impact of VEGF gene polymorphisms on clinical outcome and toxicity was briefly reviewed.