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 16 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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“…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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“…While radiation delivery optimization and dose reduction preserves vital tissue proximal to the primary tumor site, posterior fossa irradiation and on-target off-tumor effects of chemotherapy remain important considerations for therapeutic development ( 19 , 20 ). Targeting proteins involved in resolving DNA damage from either ionizing radiation (IR) induced single and double strand breaks (SSBs and DSBs) or adducts formed by chemotherapies could permit lower therapeutic dosing and more effective targeting of tumor cells ( 21 ).…”

Section: Dna Damage Signalingmentioning

confidence: 99%

Medulloblastoma and the DNA Damage Response

et al. 2022

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Medulloblastoma (MB) is the most common malignant brain tumor in children with standard of care consisting of surgery, radiation, and chemotherapy. Recent molecular profiling led to the identification of four molecularly distinct MB subgroups – Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4. Despite genomic MB characterization and subsequent tumor stratification, clinical treatment paradigms are still largely driven by histology, degree of surgical resection, and presence or absence of metastasis rather than molecular profile. Patients usually undergo resection of their tumor followed by craniospinal radiation (CSI) and a 6 month to one-year multi-agent chemotherapeutic regimen. While there is clearly a need for development of targeted agents specific to the molecular alterations of each patient, targeting proteins responsible for DNA damage repair could have a broader impact regardless of molecular subgrouping. DNA damage response (DDR) protein inhibitors have recently emerged as targeted agents with potent activity as monotherapy or in combination in different cancers. Here we discuss the molecular underpinnings of genomic instability in MB and potential avenues for exploitation through DNA damage response inhibition.

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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 16 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

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

Medulloblastoma and the DNA Damage Response

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