The Underestimated Role of Mast Cells in the Pathogenesis of Rhinopathies

Mast cells (MCs) are involved in several biological processes, such as defense against pathogens, immunomodulation, tissue repair after injury, and angiogenesis. MCs have been shown to change from protective immune cells to potent pro-inflammatory cells, influencing the progression of many pathological conditions, including autoimmune diseases and cancers. The role of MCs in the pathogenesis of rhinopathies has often been underestimated, since previous studies have focused their attention on eosinophils and neutrophils, while MCs were considered involved exclusively in allergic rhinitis. However, recent nasal cytology findings have shown the involvement of MCs in several rhinopathies, such as NARMA, NARESMA, and CRSwNP. These recent evidences highlight the crucial role that MCs play in orchestrating the inflammation of the nasal mucosa, through complex biological mechanisms, not yet fully understood. In this context, a better understanding of these mechanisms is fundamental for practicing Precision Medicine, which requires careful population selection and stratification into subgroups based on the phenotype/endotype of the patients, in order to guarantee the patient a tailored therapy. Based on this background, further studies are needed to understand the pathophysiological mechanisms involving MCs and, consequently, to develop targeted therapies aimed to obtain a selective inhibition of tissue remodeling and preventing MC-mediated immune suppression.

SYS-Mut: Decoding the Functional Significance of Rare Somatic Mutations in Cancer

Current tailored-therapy efforts in cancer are largely focused on a small number of highly recurrently-mutated driver genes but therapeutic targeting of these oncogenes remains challenging. On the other hand, the vast number of genes mutated infrequently across cancers have received less attention, in part, due to a lack of understanding of their biologic significance. Here we present SYS-Mut, a systems biology platform that can robustly infer the biologic consequences of somatic mutations by integrating routine multi-omic profiles in primary tumors. We established the accuracy of SYS-Mut by recapitulating the functional impact of known driver genes in PanCancer datasets. Subsequent application of SYS-Mut on low-frequency gene mutations in Head and Neck Cancers (HNSC), followed by molecular and pharmacogenetic validation, revealed the lipidogenic network as a novel therapeutic vulnerability in aggressive HNSC. SYS-Mut is thus a robust scalable framework that enables discovery of new targetable avenues in cancer.

SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy

One year on from the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine has made several steps towards increasing the therapeutic options against its treatment. Despite the lack of specific therapies, international societies have introduced new guidelines and launched several trials to test the efficacy of new protocols and drugs. Drug repurposing has been a fundamental strategy to find quick ways to fight the pathogen, even if it is new compounds that are drawing the attention of the scientific community. Tailored therapy should be considered to be a milestone in treatment in order to increase drug efficacy and to reduce drug toxicity. Therefore, both drug characteristics (i.e., pharmacokinetic, pharmacodynamic and safety) and the patient characteristics (i.e., stage of disease, comorbidity, concomitant treatments and the mutation of single nucleotides) could represent the key to achieving this objective. In the present study we performed a narrative review of the pharmacological treatment used to date in the management of coronavirus disease 2019 (COVID-19).

Successful Management of Pseudohypoparathyroidism Type 1b in Pregnancy: A Case Report

Pseudohypoparathyroidism (PHP) refers to broad spectrum of genetic diseases characterized by peripheral resistance to Parathormone (PTH). This condition leads to hypocalcaemia, hyperphosphatemia and elevated PTH concentrations. There is scant literature on PHP in pregnancy with 9 cases published. The treatment of the disease in pregnant women is challenging and the main target is to avoid hyper/hypocalcemia to prevent maternal adverse effects and to protect fetal parathyroid glands development. We report a rare case of PHP type 1b in pregnant woman treated with a tailored therapy.

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.