| Role of Enzymes in Cancer; Immunopharmacological Implications to Hypoxic Tumor Microenvironment |
| Paper ID : 1256-IGA |
| Authors |
|
nazila bahmaie *1, Ahmet Kilic1, Sukran Erten2, Ender Simsek1, Ozen Ozensoy Guler3 1Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University (AYBU), 06800 Ankara, Turkey. 2Division of Rheumatology, Department of Internal Medicine, Ankara Bilkent City Hospital, 06800 Ankara, Turkey. Department of Internal Medicine, Faculty of Medicine, Ankara Yildirim Beyazit University (AYBU), 06800 Ankara, Turkey. 3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University (AYBU), 06800 Ankara, Turkey |
| Abstract |
| Despite a substantial progress in the development of strategies against cancer, it still remains as a major global health issue due to a high recurrence/metastasis rate, leading basic medical scientists and clinical specialists toward more efficient diagnostics, prognostics, and therapeutics. Therefore, there is an imperative need for a comprehensive understanding on the molecular metabolism and biochemical functionalities of enzymes involved in the tumor microenvironment (TME). Pleotropic activities of hepatic vitamin D-25-hydroxylases, as well as renal D 1-hydroxylase, as well as the expression of Vitamin D Receptor (VDR), can play an indispensable role in the revolutionizing cancer management by offering a real-time monitoring of tumor dynamics, evolution of resistance mechanisms, regulating the immune system, enhancing the differentiation of monocytes into macrophages, promoting the production of anti-inflammatory cytokines, and modulating T cell responses, eventually diminishing the tumor progression-associated pro-inflammatory responses. Moreover, the interplay between vitamin Vit D and CA IX, has garnered an attention due to their respective roles in cancer immunobiology, immune responses, as well as potential therapeutic strategies. Overexpressed CA IX, regulated by hypoxia-inducible factors (HIFs), contributes to a maintained pH balance, facilitates the immune evasion, inhibiting the function of cytotoxic T lymphocytes, inducing angiogenesis, and allowing tumors to escape immune surveillance. Totally, dose-dependent effects of VDR may inhibit or lower the expression of CA IX, leading to a less acidic environment, and restoring the effectiveness of immune responses against tumors. Understanding the interactions between cofactors in the biochemical structure of metabolic enzymes or coenzymes associated to cancer metabolism rewiring, could be utilized in favor of more effective therapeutics, or prognostics for tumor progression and response to therapy in patients with cancer. It necessitates further investigations and an interdisciplinary collaboration among basic medical scientists and oncologists to address the current gaps in precisely improving patient-care and optimized clinical outcomes. |
| Keywords |
| BIOMARKER, CARBONIC ANHYDRASE, TUMOR BIOLOGY, VITAMIN D, |
| Status: Accepted |
