Special Issue "Pleiotropic Action of Selenium in the Treatment of Cancer and Related Diseases 2.0"
Deadline for manuscript submissions: 30 November 2021.
Interests: HIFs; TGF-b; oncogenic microRNA-210 druggable targets; mechanism-based biologic and cytotoxic therapies; COVID-19 and selenium
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Targeted therapies alone and in combination with chemotherapy have made significant advances in the treatment of patients with advanced cancers. However, the majority of patients remain unresponsive, with de novo and/or acquired resistance with no cures. Although human tumors and their associated microenvironment are molecularly, histologically, and immunologically heterogeneous, microRNAs (miRs), hypoxia-inducible factor 1a and HIF2a (HIFs), and transforming growth factor-beta (TGF-b) are ubiquitously over expressed in the majority of advanced cancers. Collectively, oncogenic miRs, HIFs, and TGF-b regulate multiple target genes implicated in increased tumor angiogenesis, metastasis, and drug resistance. The altered expression of these specific biomarkers in the tumor microenvironment (TME) and associated tumor cells likely contributes to the unstable, permeable tumor vasculature limiting the delivery of therapeutically effective drug concentrations to tumor tissues, and thus to tumor cell resistance. The TME is therefore the gatekeeper and tumor cells are the ultimate therapeutic target. Thus, to further advance the quality and quantity of responses achieved with the present standard therapies, future combination treatment strategies should include molecules that contribute to the stabilization of the TME followed sequentially with drugs that target tumor cells. Selenium-containing molecules such as Se-methylselenocysteine (MSC), selene-l-methionine (SLM), and selenized yeast, among others, have been shown to target and modulate biomarkers expressed in tumor cells and their associated microenvironment. Pretreatment with a defined dose and schedule of MSC or SLM has resulted in the stabilization of tumor vasculature, selective increase in drug delivery to tumor cells, and the downregulation of miRs, HIFs, and TGF-b. Administration of anticancer therapeutics when the optimal effects of selenium were achieved resulted in therapeutic synergy. This new and novel strategy is being verified in patients with advanced clear cell renal cell carcinoma with very promising results. Recent data seems to associate baseline selenium concentrations with the incidence and recovery from of COVID-19. With the pleiotropic effects of selenium as a molecular and immunologic modulator, low-cost dietary selenium supplementation may be used to enhance the efficacy of drugs and vaccines in patients with COVID-19.
This Special Issue is devoted to soliciting contributions that preclinically or clinically document the therapeutic value that can be derived from agents that target specific miRs, HIFs, and TGF-β individually and/or collectively. The collection of contributions should provide a comprehensive overview of the biology, mechanism of action, and therapeutic potential of inhibitors that target miRs, HIFs, and TGF-b in vitro as well as translated and validated in vivo models. Contributions are also solicited that expand on the potential role of selenium alone and in combination with vaccine in the treatment of COVD-19.
Prof. Dr. Youcef M. Rustum
Manuscript Submission Information
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- oncogenic microRNA-210 druggable targets
- mechanism-based biologic and cytotoxic therapies
- COVID-19 and selenium