Prospects of POLD1 in Human Cancers: A Review

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.

Expression of “DNA damage response” pathway genes in diffuse large B‐cell lymphoma: The potential for exploiting synthetic lethality

“…FEN1 has been targeted in the development of small‐molecule inhibitors for the treatment of pancreatic cancer 25 . PLOD1 has been targeted in the development of anti‐PLOD1 antibodies for the treatment of lung cancer 26 . PCNA has been targeted in developing small‐molecule inhibitors for treating colorectal and pancreatic cancer 27 .…”

“…25 PLOD1 has been targeted in the development of anti-PLOD1 antibodies for the treatment of lung cancer. 26 PCNA has been targeted in developing small-molecule inhibitors for treating colorectal and pancreatic cancer. 27 RAD51 has been targeted in the development of RAD51 inhibitors for the treatment of breast and ovarian cancer.…”

Modeling the Dynamics of Negative Mutations for a Mouse Population and the Inverse Problem of Determining Phenotypic Differences in the First Generation

“…Figure 4b shows the curves ( 14) and the result of the function q(x) ≡ q inv (x) retrieval for the specified model parameters. The curves (14) in the top picture cover only part of the region (x, t) ∈ [0, 20] × [0, 20], and the solution q inv (x) reproduces the model function q model (x) quite well only in the area covered by the model curves (14).…”

“…The catalytic and corrective subunit of the DNA polymerase δ complex, POLD1, plays a crucial role in the processes of DNA replication and repair [13]. Mutations in POLD1 are associated with abnormal cell division in various human tumors [14]. However, the significance of altered POLD1 expression in cancer and its usefulness as a prognostic factor are not fully understood [15].…”

Altered immunoexpression of DNA polymerase delta 1 catalytic subunit (POLD1) in colorectal cancer

“…Polymerase delta 1 catalytic subunit and POLE possess DNA polymerase and 3'-5' exonuclease activities, and they serve in the mechanisms of DNA repair [8]. Genetic alterations of exonuclease domains of POLD1 and POLE may affect their DNA proofreading ability and are considered factors in the development of several human neoplastic diseases including hereditary and sporadic colorectal tumours [8][9][10]. Pathologic variants of POLD1 and POLE can result in deficient DNA replication and repair predisposing to colorectal polyposis and subsequent neoplastic transformation [11,12].…”