Poly-ADP-ribose polymerases (PARPs) as a therapeutic target in the treatment of selected cancers

Przybyciński, Jarosław; Nalewajska, Magdalena; Marchelek-Myśliwiec, Małgorzata; Dziedziejko, Violetta; Pawlik, Andrzej

doi:10.1080/14728222.2019.1654458

Cited by 24 publications

(12 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, many clinical trials have demonstrated that various human malignancies with BRCA mutations, respond well to PARP inhibitors. 35 A recent study reported tha t BRCA2 alterations were potential targets in SBA. 10 Our results once again confirmed the finding and further uncovered that BRCA1 mutations were novel important targetable candidates in SBA.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma

Pan

Cheng

Wang³

et al. 2021

Cancer Science

View full text Add to dashboard Cite

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next‐generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C‐KIT mutations were the most common targets of highest‐level actionable alterations. In DNA mismatch repair–proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild‐type/nondisruptive mutations (KRASmut/TP53wt/non‐dis) were independently associated with an inferior recurrence‐free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94‐9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma

Pan

Cheng

Wang³

et al. 2021

Cancer Science

View full text Add to dashboard Cite

show abstract

“…There is a growing number of studies pointing out the potential benefit of PARPi treatment in other DDR genes deficiency outside BRCA mutations (e.g., ATM, ATR, BARD1, BRIP1, CHK1, CHK2, PALB2, RAD51 or FANC) or combination treatment with other chemotherapeutics and targeted therapy. For more information, the reader is referred to other excellent up to date reviews focused on PARP and its inhibitors [144][145][146][147][148]. However, in vitro and in vivo evidence suggest that mutations in PARP1 abolishing the DNA binding cause the resistance towards PARPi [149].…”

Section: Base Excision Repairmentioning

confidence: 99%

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Tomášová

Čumová

Šeborová

et al. 2020

Cancers

View full text Add to dashboard Cite

There is ample evidence for the essential involvement of DNA repair and DNA damage response in the onset of solid malignancies, including ovarian cancer. Indeed, high-penetrance germline mutations in DNA repair genes are important players in familial cancers: BRCA1, BRCA2 mutations or mismatch repair, and polymerase deficiency in colorectal, breast, and ovarian cancers. Recently, some molecular hallmarks (e.g., TP53, KRAS, BRAF, RAD51C/D or PTEN mutations) of ovarian carcinomas were identified. The manuscript overviews the role of DNA repair machinery in ovarian cancer, its risk, prognosis, and therapy outcome. We have attempted to expose molecular hallmarks of ovarian cancer with a focus on DNA repair system and scrutinized genetic, epigenetic, functional, and protein alterations in individual DNA repair pathways (homologous recombination, non-homologous end-joining, DNA mismatch repair, base- and nucleotide-excision repair, and direct repair). We suggest that lack of knowledge particularly in non-homologous end joining repair pathway and the interplay between DNA repair pathways needs to be confronted. The most important genes of the DNA repair system are emphasized and their targeting in ovarian cancer will deserve further attention. The function of those genes, as well as the functional status of the entire DNA repair pathways, should be investigated in detail in the near future.

show abstract

“…Clinically approved PARP inhibitors include olaparib, rucaparib, and talazoparib. New PARP inhibitors with more DNA trapping potential, superior safety profiles, or enhanced combination therapies could be introduced to the clinical setting in the future [ 75 ]. Synthetic lethal anticancer treatments including PARP inhibitors can target tumor cells with specific HR defects.…”

Section: Cdk/parp and Ddrmentioning

confidence: 99%

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Kciuk

Gielecińska

Mujwar

et al. 2022

IJMS

View full text Add to dashboard Cite

Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.

show abstract

Poly-ADP-ribose polymerases (PARPs) as a therapeutic target in the treatment of selected cancers

Cited by 24 publications

References 104 publications

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Contact Info

Product

Resources

About