PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

Abstract

Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis. Up until now, PARP1 inhibitors are clinically used not only for monotherapy to suppress various tumors, but also for adjuvant therapy, to maintain or enhance therapeutic effects of mature antineoplastic drugs, as well as protect patients from chemotherapy and surgery-induced injury. To supply a framework for understanding recent research progress of PARP1 in carcinomas, we review the structure, expression, functions, and mechanisms of PARP1, and summarize the clinically mature PARP1-related anticancer agents, to provide some ideas for the development of other promising PARP1 inhibitors in antineoplastic therapy.

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

“…In fact, evidence that supports both a tumor promoter and suppressor function of SIRT1 has been reported for TNBC and luminal breast cancer subtypes [142]. Concerning PARP1, its up-regulation has been reported in multiple cancers, while its inhibition has the capacity to suppress angiogenesis, metastasis, and tumor-induced inflammation [48].…”

“…As previously mentioned, NAM increases the levels of NAD + , boosts energy metabolism and protects cells from oxidative stress [39]. NAM also inhibits SIRT1 and PARP1, both of which have been shown to be up-regulated in multiple cancers [39,48,[137][138][139]. However, while it suppresses Despite the aforementioned evidence, more studies are needed to unravel NAM's entire molecular mechanism in diverse cancer scenarios, before its widespread implementation into clinical practice.…”

“…Biomolecules 2020, 10, 477 3 of 21 SIRT1-mediated deacetylation of target proteins, low NAD + /NADH ratio diminishes SIRT1 activity [47]. PARP1, triggered by DNA damage (strand breaks), enhances DNA repair and maintains genome stability [40,48]. Of interest, mild and moderate genetic damage facilitate DNA repair or apoptosis, respectively; however, severe damage leads to PARP1 overactivation that depletes NAD + and ATP leading to necrosis [40,47].…”

Synthesis and Anti‐Proliferative Activity of a Triazole‐Fused Thymidine Analogue

“…Earlier reports have shown that PARP1 is over expressed in solid cancerous tissues . Integrating the in vitro and in silico results there is a possibility of PARP1 inhibition mediated cancer cell death .…”

PARP1 (poly(ADP-ribose) polymerase 1)

“…In addition to malignant tissues of BRCA-mutant, triple-negative, and receptor-positive breast carcinoma, PARP1 is overexpressed significantly in uterine carcinoma and ovarian carcinoma. As in breast carcinoma, ovarian cancer cells show high sensitivity to drugs designed for PARP1 inhibition (Iqbal et al, 2012;Thompson & Easton, 2003;L. Wang et al, 2017).…”