TRAIL-mediated signaling in bladder cancer: realization of clinical efficacy of TRAIL-based therapeutics in medical oncology
Farooqi A.A. Venera R. Kapanova G. Tanbayeva G. Akhmetova G. Kudabayev Y. Turgambayeva A.
August 2023Springer
Medical Oncology
2023#40Issue 8
Bladder cancer is a therapeutically challenging disease and wealth of knowledge has enabled researchers to develop a clear understanding of mechanisms which underlie carcinogenesis and metastasis. Excitingly, research over decades has unveiled wide-ranging mechanisms which serve as central engine in progression of bladder cancer. Loss of apoptosis, drug resistance, and pro-survival signaling are some of the highly studied cellular mechanisms. Therefore, restoration of apoptosis in resistant cancers is a valuable and attractive strategy. Discovery of TRAIL-mediated signaling cascade is an intriguing facet of molecular oncology. In this review, we have provided an overview of the translational and foundational advancements in dissecting the genomic and proteomic cartography of TRAIL signaling exclusively in the context of bladder cancer. We have also summarized how different natural products sensitized drug-resistant bladder cancer cells to TRAIL-mediated apoptosis. Interestingly, different death receptors that activate agonistic antibodies have been tested in various phases of clinical trials against different cancers. Certain clues of scientific evidence have provided encouraging results about efficacy of these agonistic antibodies (lexatumumab and mapatumumab) against bladder cancer cell lines. Therefore, multipronged approaches consisting of natural products, chemotherapeutics, and agonistic antibodies will realistically and mechanistically provide proof-of-concept for the translational potential of these combinatorial strategies in well-designed clinical trials.
Apoptosis , Cancer , Cell signaling , TRAIL
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Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan
Medical University of Astana, Astana, Kazakhstan
Al-Farabi Kazakh National University, Almaty, 71 al-Farabi Ave, Almaty, 050040, Kazakhstan
Scientific Center of Anti-infectious Drugs, Kazakhstan, 75 a al-Faraby Ave, Almaty, 050040, Kazakhstan
City Polyclinic No. 21 of Almaty, Almaty, Kazakhstan
Department Public Health and Management, NJSC, Astana Medical University, Astana, Kazakhstan
Department of Molecular Oncology
Medical University of Astana
Al-Farabi Kazakh National University
Scientific Center of Anti-infectious Drugs
City Polyclinic No. 21 of Almaty
Department Public Health and Management
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