DNA polymerase eta: A potential pharmacological target for cancer therapy.
J Cell Physiol
; 236(6): 4106-4120, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33184862
ABSTRACT
In the last two decades, intensive research has been carried out to improve the survival rates of cancer patients. However, the development of chemoresistance that ultimately leads to tumor relapse poses a critical challenge for the successful treatment of cancer patients. Many cancer patients experience tumor relapse and ultimately die because of treatment failure associated with acquired drug resistance. Cancer cells utilize multiple lines of self-defense mechanisms to bypass chemotherapy and radiotherapy. One such mechanism employed by cancer cells is translesion DNA synthesis (TLS), in which specialized TLS polymerases bypass the DNA lesion with the help of monoubiquitinated proliferating cell nuclear antigen. Among all TLS polymerases (Pol η, Pol ι, Pol κ, REV1, Pol ζ, Pol µ, Pol λ, Pol ν, and Pol θ), DNA polymerase eta (Pol η) is well studied and majorly responsible for the bypass of cisplatin and UV-induced DNA damage. TLS polymerases contribute to chemotherapeutic drug-induced mutations as well as therapy resistance. Therefore, targeting these polymerases presents a novel therapeutic strategy to combat chemoresistance. Mounting evidence suggests that inhibition of Pol η may have multiple impacts on cancer therapy such as sensitizing cancer cells to chemotherapeutics, suppressing drug-induced mutagenesis, and inhibiting the development of secondary tumors. Herein, we provide a general introduction of Pol η and its clinical implications in blocking acquired drug resistance. In addition; this review addresses the existing gaps and challenges of Pol η mediated TLS mechanisms in human cells. A better understanding of the Pol η mediated TLS mechanism will not merely establish it as a potential pharmacological target but also open possibilities to identify novel drug targets for future therapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores da Síntese de Ácido Nucleico
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DNA Polimerase Dirigida por DNA
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Replicação do DNA
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article