Cutaneous melanoma arises from proliferating melanocytes, cells specialized in the production of melanin. This property means melanin can be considered as a target for monitoring melanoma patients using nuclear imaging or targeted radionuclide therapy (TRT). Since the 1970s, many researchers have shown that specific molecules can interfere with melanin. This paper reviews some such molecules benzamide structures improved to increase their pharmacokinetics for imaging or TRT. We first describe the characteristics and biosynthesis of melanin, and the main features of melanin tracers. The second part summarizes the preclinical and corresponding clinical studies on imaging. The last section presents TRT results from ongoing protocols and discusses combinations with other therapies as an opportunity for melanoma non-responders or patients resistant to treatments.Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.Diabetes mellitus is associated with endothelial dysfunction that leads to cardiovascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrated efficacy in glycemic control in type 2 diabetes patients with positive cardiovascular outcome. Recent research revealed a link between SGLT2 inhibition and improved macro- and microvascular endothelial functions. Mechanisms underlying this phenomenon could be due to the role of SLGT2 in the regulation of endothelial physiology. In this review, current knowledge and hypothesis on the link between SGLT2 and endothelial function were critically appraised and the impact of SGLT2 inhibitors on endothelial dysfunction in pre-clinical and clinical studies was discussed.Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. TP-1454 clinical trial We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology.Cystic Fibrosis (CF) lung disease results from mutations in the CFTR anion channel that reduce anion and fluid secretion by airway epithelia. Impaired secretion compromises airway innate defence mechanisms and leads to bacterial colonization, excessive inflammation and tissue damage; thus, restoration of CFTR function is the goal of many CF therapies. CFTR channels are activated by cyclic nucleotide-dependent protein kinases. The second messengers 3’5′-cAMP and 3’5′-cGMP are hydrolysed by a large family of cyclic nucleotide phosphodiesterases that provide subcellular spatial and temporal control of cyclic nucleotide-dependent signalling. Selective inhibition of these enzymes elevates cyclic nucleotide levels, leading to activation of CFTR and other downstream effectors. Here we examine members of the PDE family that are likely to regulate CFTR-dependent ion and fluid secretion in the airways and discuss other actions of PDE inhibitors that can influence cyclic nucleotide-regulated mucociliary transport, inflammation and bronchodilation. Finally, we review PDE inhibitors and the potential benefits they could provide as CF therapeutics.Medulloblastoma is the most common malignant CNS tumor of childhood, affecting ~350 patients/year in the USA. In 2020, most children are cured of their disease, however, survivors are left with life-long late-effects as a consequence of intensive surgery, and application of chemo- and radio-therapy to the developing brain. A major contributor to improvements in patient survival has been the development of risk-stratified treatments derived from a better understanding of the prognostic value of disease biomarkers. The characterization and validation of these biomarkers has engendered a comprehensive understanding of the extensive heterogeneity that exists within the disease, which can occur both between and within tumors (inter- and intra-tumoral heterogeneity, respectively). In this review, we discuss inter-tumoral heterogeneity, describing the early characterization of clinical and histopathological disease heterogeneity, the more recent elucidation of molecular disease subgroups, and the potential for novel therapies based on specific molecular defects.