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Mitochondria, organelles surrounded by a double membrane and with their own small genome, are the cells’ energy centers. Besides the production of ATP through cellular respiration, mitochondria play a pivotal role in other aspects of the life and death of a cell: heat production, programmed cell death, the regulation of metabolic activity, immunity, and calcium homeostasis. A number of diseases are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory, and metabolic disorders as well as cancer. Mitochondria therefore represent an important therapy target, and it is not surprising that a number of different treatment strategies have emerged. Approaches targeting mitochondria can be split into two opposite categories: drugs that restore mitochondrial function and drugs that trigger mitochondria-mediated cell death. Targeted drug delivery to achieve the selective accumulation of drug molecules in mitochondria is complex and involves methods such as direct drug modification or encapsulation into nanocarriers.

retinal ischemia --- blood–brain barrier --- endothelial --- reactive oxygen species --- oxidative stress --- tunneling nanotubules --- neuron --- central nervous system --- inflammation --- hypoxia --- anticancer peptide (ACP) --- antimicrobial peptide (AMP) --- anticancer peptides --- antimicrobial peptides --- host defense peptides --- prediction --- random forest --- mitochondria --- mitochondrial DNA --- mitochondrial disorders --- pharmacological therapy --- gene therapy --- precision medicine --- cardiovascular disease --- drug delivery --- mitochondria dysfunctions --- nanocarriers --- oxoglutarate carrier --- malate-aspartate shuttle --- cancer metabolism --- ATP production --- diphenyleneiodonium --- NADPH-oxidase --- differentiation --- proliferation --- mitochondria-targeted antioxidants --- LPS --- mitochondrial ROS --- antitumor agents --- fluorescence lifetime imaging --- medicinal chemistry --- metabolic drug --- mitochondrial carrier --- melanoma --- plumbagin --- cytotoxic effect --- metabolism --- cholesterol --- lipid raft --- mitochondrial permeability transition pore --- alkylphospholipid analog --- edelfosine --- mitochondrial oncometabolites --- cancer drug resistance --- mitochondrial disease --- heteroplasmy --- mitochondrial gene delivery --- n/a --- blood-brain barrier

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Malignant mesothelioma (MM) is a rare and aggressive cancer, related to chronic inflammation and oxidative stress caused mainly by exposure to asbestos. Although this mineral has been banned for decades in many countries, epidemiologists predict the MM epidemic will last past 2040, raising many concerns in public health given its late diagnosis, dismal prognosis, and lack of current efficient therapies.To deal with this situation, important breakthroughs have recently been made in the understanding of MM’s complex biology and the carcinogenic process of the different patterns of the disease. Examples of these include the development of new biomarkers and the deciphering of gene–environment interactions, molecular mechanisms of invasiveness, deregulated pathways, altered expression of miRNAs, DNA damage repair, or metabolic profile. From now on, MM’s aggressive and chemoresistant character appears linked to a polyclonal malignancy, and heterogeneity in molecular alterations.Given these improvements, new therapeutic targets are being explored to solve the double challenge faced by clinicians. The first is to reduce tumor development and its wasting consequences as soon as possible, without resistance and with limited toxicity. The second is to stimulate the recognition of tumor cells by the induction of a specific immune response. This Special Issue will highlight all these aspects.

well-differentiated papillary mesothelioma --- WDPM --- malignant mesothelioma --- DNA sequencing --- mutation --- mesothelioma --- tumor suppressor --- targeted therapy --- immunotherapy --- biomarkers --- proteomics --- macrophage-capping protein --- fatty acid-binding protein --- laminin subunit beta-2 --- selenium-binding protein 1 --- carcinogenesis --- malignant pleural mesothelioma --- asbestos exposure --- DNA methylation --- lymphocyte-to-monocyte ratio --- epigenome-wide analysis --- survival analysis --- metabolomics --- radiotherapy --- cancers --- inflammation --- infiltrating immune cells --- prognostic biomarker --- predictive biomarker --- immune therapy --- VATS --- extrapleural pneumonectomy --- pleurectomy decortication --- therapy response --- survival --- FDG --- PET-CT --- mesothelium --- oxidative stress --- redox-sensitive factors --- asbestos --- carbon nanotubes --- protein-protein interactions --- systems biology --- network analysis --- drug repurposing --- pleural mesothelioma --- gene expression --- immunogenicity --- sarcomatoid --- epithelioid --- first line --- meta-analysis --- systematic review --- MPM --- lurbinectedin --- DNA damage response --- histotype --- Hippo pathway --- NF2 --- BAP1 --- CDKN2A --- PTCH1 --- SETD2 --- MTAP --- liquid biopsies --- circulating tumor DNA --- plasma --- cancer-specific mutations --- genomics --- cancer biomarkers --- tumor microenvironment --- tumor-associated macrophages --- dendritic cells --- immunohistochemistry --- interaction analysis --- pleural effusion --- n/a