Akademik Veri Yönetim Sistemi
10. International Congress of Molecular Medicine, İzmir, Türkiye, 23 - 27 Eylül 2024, ss.56, (Özet Bildiri)
Metabolic reprogramming is a fundamental characteristic of cancer cells, facilitating
sustained proliferation, metastasis, and resistance to chemotherapy in a nutrient-deficient
microenvironment. Consequently, targeting these metabolic alterations has emerged as a
promising strategy for overcoming chemoresistance and treating various cancer types, with
extensive research on metabolic inhibitors over the past two decades. Key metabolic pathways,
including aerobic glycolysis, the pentose phosphate pathway (PPP), fatty acid synthesis,
glutamine metabolism, redox homeostasis, oxidative phosphorylation (OXPHOS), nucleotide
metabolism, and mitochondrial function—play critical roles in cancer initiation, progression,
metastasis, angiogenesis, chemoresistance, and the modulation of the tumor microenvironment
(TME). By applying small molecules and enzyme inhibitors, interventions aimed at these
pathways have been shown to activate novel cell death mechanisms such as ferroptosis,
parthanatos, NETosis, pyroptosis, necroptosis, and cuproptosis. For example, according to
preclinical and clinical studies, statins, including lovastatin and atorvastatin, which inhibit the
mevalonate pathway, have demonstrated efficacy in promoting remission in various
malignancies, including ovarian cancer, lymphoma, and leukemia. Moreover, extensive
investigations have been conducted into inhibitors targeting glycolysis, the PPP, and redox
metabolism, specifically hexokinase inhibitors, across multiple cancer types, such as ovarian,
prostate, pancreatic, lung, stomach, brain, and colorectal cancers.
These findings underscore the critical role of metabolic reprogramming in cancer
biology and the potential of metabolic targeting as a therapeutic approach. Several factors, such
as tumor heterogeneity, plasticity, adverse effects, and the interactions between the tumor
microenvironment (TME) and the tumor itself, pose significant challenges to the efficacy of
metabolic targeting therapies. These complexities often contribute to the unsatisfactory
outcomes observed in clinical settings. It is essential to identify more accurate and relevant
metabolic targets to enhance the precision and effectiveness of metabolic targeting strategies
and better elucidate the intricate metabolic landscape of tumors