The role of DNA damage response in chemo- and radio-resistance of cancer cells: Can DDR inhibitors sole the problem?

Sadoughi, Fatemeh; Mirsafaei, Liaosadat; Dana, Parisa Maleki; Hallajzadeh, Jamal; Asemi, Zatollah; Mansournia, Mohammad Alì; Montazer, Majid; Hosseinpour, Mohammad; Yousefi, Bahman

doi:10.1016/j.dnarep.2021.103074

Cited by 18 publications

(12 citation statements)

References 97 publications

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“…As a key component of the tumor extracellular matrix, type I collagen shows high density and distorted architecture in malignant cancer, linking it to tumor formation and metastasis [ 83 ]. Therefore, the discovery of DDRs as collagen receptors represents a new target in the regulation of tumor progression [ 84 , 85 , 86 , 87 , 88 , 89 ].…”

Section: Role Of Ddr In Cancermentioning

confidence: 99%

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

Elkamhawy

Nada

et al. 2021

IJMS

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Discoidin domain receptor (DDR) is a collagen-activated receptor tyrosine kinase that plays critical roles in regulating essential cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. As a result, DDR dysregulation has been attributed to a variety of human cancer disorders, for instance, non-small-cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, and breast cancer, in addition to some inflammatory and neurodegenerative disorders. Since the target identification in the early 1990s to date, a lot of efforts have been devoted to the development of DDR inhibitors. From a medicinal chemistry perspective, we attempted to reveal the progress in the development of the most promising DDR1 and DDR2 small molecule inhibitors covering their design approaches, structure-activity relationship (SAR), biological activity, and selectivity.

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Section: Role Of Ddr In Cancermentioning

confidence: 99%

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

Elkamhawy

Nada

et al. 2021

IJMS

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“…It has been well established that tumor cells that initially show a good therapeutic response to RT and later often develop resistance to treatment. Differential radiosensitivity and induction of radioresistance have been associated with altered responses to DNA damage and repair of DNA double-strand breaks (DSBs) [ 11 , 12 ]. Among other factors, particular hypoxia has an important impact on RT resistance [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma

Gravina

Colapietro

Mancini

et al. 2022

Cancers

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Cell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs). Their sensitivity to ATX-101 was not related to cellular levels of PCNA, or p53, PTEN, or MGMT status. However, ATX-101 reduced Akt/mTOR and DNA-PKcs signaling, and a correlation between high Akt activation and sensitivity for ATX-101 was found. ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with radiotherapy (RT). In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.

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“…In the following, we will discuss the role of noncoding RNAs in drug resistance. Further details regarding the role of DNA repair in the failure of cancer chemotherapy have also been extensively described elsewhere [50]. Inhibition of some signaling pathways using different inhibitors has also had positive results in attenuating drug resistance in cancer cells.…”

Section: Advances In the Study Of Drug Resistance Inhibition To Enhan...mentioning

confidence: 99%

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

et al. 2022

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The CRISPR/Cas9 system is an RNA-based adaptive immune system in bacteria and archaea. Various studies have shown that it is possible to target a wide range of human genes and treat some human diseases, including cancers, by the CRISPR/Cas9 system. In fact, CRISPR/Cas9 gene editing is one of the most efficient genome manipulation techniques. Studies have shown that CRISPR/Cas9 technology, in addition to having the potential to be used as a new therapeutic approach in the treatment of cancers, can also be used to enhance the effectiveness of existing treatments. Undoubtedly, the issue of drug resistance is one of the main obstacles in the treatment of cancers. Cancer cells resist anticancer drugs by a variety of mechanisms, such as enhancing anticancer drugs efflux, enhancing DNA repair, enhancing stemness, and attenuating apoptosis. Mutations in some proteins of different cellular signaling pathways are associated with these events and drug resistance. Recent studies have shown that the CRISPR/Cas9 technique can be used to target important genes involved in these mechanisms, thereby increasing the effectiveness of anticancer drugs. In this review article, studies related to the applications of this technique in overcoming drug resistance in cancer cells will be reviewed. In addition, we will give a brief overview of the limitations of the CRISP/Cas9 gene-editing technique.

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The role of DNA damage response in chemo- and radio-resistance of cancer cells: Can DDR inhibitors sole the problem?

Cited by 18 publications

References 97 publications

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

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