Nucleases as molecular targets for cancer diagnosis

Abstract

Early cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer

“…DNA exonucleases may favour the appearance of mutations in healthy cells, converting them into tumour cells, or may be necessary for certain tumours to keep the inherent genomic instability of malignancy under control, aiding tumour cells to avoid cell death, or impact on the immune response. In this manner, aberrant DNAse activity in tumours have been suggested to be exploited as a molecular whistleblower for diagnosis [ 246 ]. Hence, these types of enzymes are promising targets for cancer treatment promoting synthetic lethality and early detection of certain types of cancer.…”

Nuclease Activity as a Biomarker in Cancer Detection

“…Biomarkers could be molecular, physiologic, histologic, or radiographic [148]. In this regard, many nucleases have been the topic of research that indicated their potential utility as diagnostic biomarkers for various cancer types such as prostate cancer [54], gynecologic cancers [149,150], breast [151,152], head and neck squamous cell carcinoma (HNSCC) [17], colorectal [153] and others as reviewed in paper I [36].…”

“…Moreover, nucleases are naturally occurring enzymes in all of the three domains of life: Bacteria, Archaea, and Eukarya [22][23][24], as intracellular [25], membrane bound [25,26] or secreted proteins [3]. The diversity of these enzymes encouraged implementation in wide applications, as tools in nucleic acid bioengineering [27], therapeutic molecular targets [28][29][30][31][32][33][34], therapeutic agents [2,25,35], and as disease biomarkers [36,37].…”

“…Nucleases are promising biomolecules in this sense. Multiple nucleases display alteration in expression and activity in correlation with cancer as reported in research and summarized in paper I [36]. Nucleases were even suggested to promote cancer, such as DNase4 in prostate cancer [54] and RNase5 in many cancers [55][56][57][58][59][60].…”

Intratumor microbiome in cancer progression: current developments, challenges and future trends

“…Cancer is a threat to human health worldwide owing to the high morbidity and mortality rates. All cancer cells are characterized by common hallmarks, including transformation, unrestricted growth, and progression [ 7 – 10 ]. Various factors have been identified that contribute to cancer initiation and progression, including gene mutations, suppressed immune responses, and a complex tumor microenvironment (TME) [ 11 – 14 ].…”