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Pozzi 1, *, Roberto Campagna 1, *, Davide Sartini 1 and Monica Emanuelli 1,2  \nCitation: Pozzi, V.; Campagna, R.; Sartini, D.; Emanuelli, M. Enzymes Dysregulation in Cancer: From Diagnosis to Therapeutical Approaches. Int. J. Mol. Sci. 2023, 24, 13815. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241813815  \nReceived: 5 September 2023  \nAccepted: 6 September 2023  \nPublished: 7 September 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Clinical Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; [d.sartini@univpm.it](d.sartini@univpm.it) (D.S.); [m.emanuelli@univpm.it](m.emanuelli@univpm.it) (M.E.)  \n2 New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, 60131 Ancona, Italy  \n* [Correspondence: v.pozzi@univpm.it](Correspondence: v.pozzi@univpm.it) (V.P.); [r.campagna@univpm.it](r.campagna@univpm.it) (R.C.)  \nThe metabolic reprogramming that occurs in cancer cells is a hallmark of cancer [1] . Indeed, elucidating the effects of dysregulated metabolism on cancer cell phenotype constitutes the focus of many researchers. Proliferating malignant cells are highly demanding in terms of energy supply and molecules required to fuel biosynthesis. Thus, cancer cells display significant metabolic alterations to meet the requirements for rapid growth and survival. For instance, cancer cells are characterized by enhanced glycolysis, the so-called“Warburg effect”, and glutamine catabolism. The reprogramming of cell metabolism toward a malignant phenotype is the result of a series of downstream events triggered by the mutations of oncogenes or tumor suppressors, dysregulated signal transduction pathways, and altered nutrient availability in the tumor microenvironment [2,3] .  \nDespite the continuous accumulation of mutations responsible for intra-and intertumor heterogeneity, the dysregulation of specific enzymes can be a distinguished feature for some groups of malignancies [4–6] . Among the enzymes that play a key role in the proliferation and aggressiveness of malignant cells there are glycolytic enzymes like lactate dehydrogenase (LDH), caspases, cyclin-dependent kinases, redox–detox enzymes and NAD+-dependent enzymes [7,8] . In recent years, several enzymes emerged as potential biomarkers for the diagnosis or prognosis of several malignancies [9–14] . Moreover, the possibility of designing specific inhibitors has also opened the possibility of utilizing these biomarkers as therapeutic targets [15–18] . The need to discover novel enzymatic pathways dysregulated in cancer, as well as identifying novel potential therapeutic targets for cancer management, was highlighted by several papers published in this Special Issue.  \nThe works published by Tossetta et al. reviewed the pathophysiology, treatment options and novel biomarkers in ovarian cancer. In particular, authors focused on the dysregulated enzymatic pathways responsible for the enhanced chemoresistance of ovarian cancer cells. The authors focused on the role of metformin, which exerts important anticancer effects in malignant cells as an inhibitor of respiratory chain complex I, which in turn oxidizes the NADH yielded through the Krebs cycle. Moreover, it has been demonstrated that this molecule significantly restores drug sensitivity in ovarian cancer cells that display resistance to paclitaxel and platinum-derived drugs [19] .  \nThe same research group reviewed the effect of the antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), whose expression is mainly regulate","cbCaicWt1C1G5AsZ","https://ap.wps.com/l/cbCaicWt1C1G5AsZ","pdf",189517,"English","# Enzymes dysregulation and cancer metabolism\n## Enzymes as biomarkers and therapeutic targets\n## Case studies in ovarian and prostate cancer","[{\"question\":\"Why is enzyme dysregulation considered important in cancer?\",\"answer\":\"The text links enzyme dysregulation to cancer metabolic reprogramming and to the downstream effects of oncogenic mutations, altered signaling, and nutrient availability that sustain proliferation and survival.\"},{\"question\":\"How can enzymes contribute to diagnosis or prognosis?\",\"answer\":\"Several enzymes are described as potential biomarkers, enabling diagnosis or prognostic assessment of malignancies.\"},{\"question\":\"What therapeutic strategies are discussed for dysregulated enzymes?\",\"answer\":\"The document emphasizes designing specific inhibitors to exploit enzyme biomarkers as therapeutic targets and describes examples of pathway inhibition to enhance chemosensitivity or block cancer-related processes.\"}]","Enzymes Dysregulation in Cancer - From Diagnosis to Therapeutical Approaches | PDF",1790563781]