Prospects of POLD1 in Human Cancers: A Review

SIMPLE SUMMARY: Polymerase delta 1 (POLD1), a catalytic and proofreading subunit of the human DNA polymerase delta (Polδ), plays a vital role in maintaining the stability of the genome. In recent years, POLD1 germline and somatic mutations, as well as gene-expression patterns, have been extensively studied in cancers. Nevertheless, the complex regulatory mechanisms of POLD1 expression and their clinical relevance are yet to be elucidated. This review aims to summarize the current research status regarding the role of POLD1 in neoplastic processes. ABSTRACT: Cancer is the second leading cause of death globally, exceeded only by cardiovascular disease. Despite the introduction of several survival-prolonging treatment modalities, including targeted therapy and immunotherapy, the overall prognosis for the metastatic disease remains challenging. Therefore, the identification of new molecular biomarkers and therapeutic targets related to cancer diagnosis and prognosis is of paramount importance. DNA polymerase delta 1 (POLD1), a catalytic and proofreading subunit of the DNA polymerase δ complex, performs a crucial role in DNA replication and repair processes. Recently, germline and somatic mutations of the POLD1 gene have been acknowledged in several malignancies. Moreover, diversified POLD1 expression profiles have been reported in association with clinicopathological features in a variety of tumor types. With this review, we aim to summarize the current knowledge on the role of POLD1 in cancers. In addition, we discuss the future prospects and clinical applications of the assessment of POLD1 mutation and expression patterns in tumors.