Browsing by Author "Peter Timashev"

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FNC: An Advanced Anticancer Therapeutic or Just an Underdog?
(Frontiers Media S.A., 2022) Daria Fayzullina; Rajesh Kumar Kharwar; Arbind Acharya; Anton Buzdin; Nicolas Borisov; Peter Timashev; Ilya Ulasov; Byron Kapomba
Azvudine (FNC) is a novel cytidine analogue that has both antiviral and anticancer activities. This minireview focuses on its underlying molecular mechanisms of suppressing viral life cycle and cancer cell growth and discusses applications of this nucleoside drug for advanced therapy of tumors and malignant blood diseases. FNC inhibits positive-stand RNA viruses, like HCV, EV, SARS-COV-2, HBV, and retroviruses, including HIV, by suppressing their RNA-dependent polymerase enzymes. It may also inhibit such enzyme (reverse transcriptase) in the human retrotransposons, including human endogenous retroviruses (HERVs). As the activation of retrotransposons can be the major factor of ongoing cancer genome instability and consequently higher aggressiveness of tumors, FNC has a potential to increase the efficacy of multiple anticancer therapies. Furthermore, FNC also showed other aspects of anticancer activity by inhibiting adhesion, migration, invasion, and proliferation of malignant cells. It was also reported to be involved in cell cycle arrest and apoptosis, thereby inhibiting the progression of cancer through different pathways. To the date, the grounds of FNC effects on cancer cells are not fully understood and hence additional studies are needed for better understanding molecular mechanisms of its anticancer activities to support its medical use in oncology. Copyright © 2022 Fayzullina, Kharwar, Acharya, Buzdin, Borisov, Timashev, Ulasov and Kapomba.
Novel Targeted Therapeutic Strategies for Ewing Sarcoma
(MDPI, 2022) Daria Fayzullina; Sergey Tsibulnikov; Mikhail Stempen; Brett A. Schroeder; Naveen Kumar; Rajesh Kumar Kharwar; Arbind Acharya; Peter Timashev; Ilya Ulasov
Ewing sarcoma (ES) is an uncommon cancer that arises in mesenchymal tissues and represents the second most widespread malignant bone neoplasm after osteosarcoma in children. Amplifications in genomic, proteomic, and metabolism are characteristics of sarcoma, and targeting altered cancer cell molecular processes has been proposed as the latest promising strategy to fight cancer. Recent technological advancements have elucidated some of the underlying oncogenic characteristics of Ewing sarcoma. Offering new insights into the physiological basis for this phenomenon, our current review examines the dynamics of ES signaling as it related to both ES and the microenvironment by integrating genomic and proteomic analyses. An extensive survey of the literature was performed to compile the findings. We have also highlighted recent and ongoing studies integrating metabolomics and genomics aimed at better understanding the complex interactions as to how ES adapts to changing biochemical changes within the tumor microenvironment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
The spectrum of cell death in sarcoma
(Elsevier Masson s.r.l., 2023) Elizaveta Belyaeva; Nina Loginova; Brett A. Schroeder; Ian S. Goldlust; Arbind Acharya; Sandeep Kumar; Peter Timashev; Ilya Ulasov
The balance between cell death and cell survival is a highly coordinated process by which cells break down and remove unnecessary or harmful materials in a controlled, highly regulated, and compartmentalized manner. Cell exposure to various stresses, such as oxygen starvation, a lack of nutrients, or exposure to radiation, can initiate autophagy. Autophagy is a carefully orchestrated process with multiple steps, each regulated by specific genes and proteins. Autophagy proteins impact cellular maintenance and cell fate in response to stress, and targeting this process is one of the most promising methods of anti-tumor therapy. It is currently not fully understood how autophagy affects different types of tumor cells, which makes it challenging to predict outcomes when this process is manipulated. In this review, we will explore the mechanisms of autophagy and investigate it as a potential and promising therapeutic target for aggressive sarcomas. © 2023 The Authors