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The Transient Receptor Potential Vanilloid type-2 (TRPV2) channel exhibits oncogenicity in different types of cancers. TRPV2 is implicated in signaling pathways that mediate cell survival, proliferation, and metastasis. In leukemia and bladder cancer, the oncogenic activity of TRPV2 was linked to alteration of its expression profile. In multiple myeloma patients, TRPV2 overexpression correlated with bone tissue damage and poor prognosis. In prostate cancer, TRPV2 overexpression was associated with the castration-resistant phenotype and metastasis. Loss or inactivation of TRPV2 promoted glioblastoma cell proliferation and increased resistance to CD95-induced apoptotic cell death. TRPV2 overexpression was associated with high relapse-free survival in triple-negative breast cancer, whereas the opposite was found in patients with esophageal squamous cell carcinoma or gastric cancer. Another link was found between TRPV2 expression and either drug-induced cytotoxicity or stemness of liver cancer. Overall, these findings validate TRPV2 as a prime candidate for cancer biomarker and future therapeutic target.

Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.

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Corticosteroids are adrenal hormones that play important physiologic roles including modulation of glucose metabolism, protein catabolism, alteration of calcium metabolism, regulation of bone turnover, suppression of immune system, and down-regulation of the inflammatory cascade. Because of their diverse effects, corticosteroids have been used therapeutically for treating a wide variety of auto-immune, rheumatologic, inflammatory, neoplastic and infectious diseases. In the field of pulmonology, corticosteroids have been used for the treatment of reactive airway diseases (such as asthma and allergic bronchopulmonary aspergillosis), chronic obstructive pulmonary disease, sarcoidosis, collagen vascular diseases (such as vasculitic disorders), eosinophilic pneumonitis, idiopathic interstitial pneumonias and infectious disorders (such as laryngotracheobronchitis). Different formulations of corticosteroids are commercially available including tablets, intravenous injections, intramuscular formulations and inhaled preparations. Long-term use of corticosteroids is often limited by their adverse effects, which include abnormal fat deposition, weight gain, diabetes mellitus, cataracts, glaucoma, osteoporosis, osteonecrosis, elevated risk of fractures, increased susceptibility to infections, proximal myopathy, depression, psychosis, adrenal atrophy with risk of Addisonian crisis, abdominal striae, acne vulgaris, delayed wound healing, easy bruising, electrolyte abnormalities and increased risk of peptic ulcer disease. As our understanding of corticosteroids advances, we may be able to identify individuals at higher risk of experiencing adverse effects.