DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Апрель 30, 2020

Abstract Radiotherapy is one of the most common countermeasures for treating a wide range tumors. However, radioresistance cancer cells still major limitation radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers improving outcomes radiotherapy. DNA double-strand breaks lethal lesions induced by ionizing radiation can trigger series cellular damage responses (DDRs), including those helping recover from injuries, such as activation sensing early transduction pathways, cell cycle arrest, repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy overcoming radioresistance, some important advances breakthroughs have already been achieved in recent years. On basis comprehensively reviewing signal we provide update on novel promising druggable emerging that be exploited radiosensitization. We further discuss identified preclinical studies, current clinical trials, application chemical inhibitors targeting key proteins, DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia–telangiectasia mutated Rad3-related), MRN (MRE11-RAD50-NBS1) complex, PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, HIF-1 (hypoxia-inducible factor-1). Challenges radiation-induced targeted therapy also discussed based achievements biological field

Язык: Английский

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DNA damage kinase signaling: checkpoint and repair at 30 years

The EMBO Journal, Год журнала: 2019, Номер 38(18)

Опубликована: Авг. 8, 2019

Язык: Английский

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Checkpoint Responses to DNA Double-Strand Breaks

Annual Review of Biochemistry, Год журнала: 2020, Номер 89(1), С. 103 - 133

Опубликована: Март 16, 2020

Cells confront DNA damage in every cell cycle. Among the most deleterious types of are double-strand breaks (DSBs), which can cause lethality if unrepaired or cancers improperly repaired. In response to DSBs, cells activate a complex checkpoint (DDC) that arrests cycle, reprograms gene expression, and mobilizes repair factors prevent inheritance broken chromosomes. Here we examine DDC, induced by budding yeast model system mammals.

Язык: Английский

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In‐depth and 3‐dimensional exploration of the budding yeast phosphoproteome

EMBO Reports, Год журнала: 2021, Номер 22(2)

Опубликована: Янв. 25, 2021

Язык: Английский

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Inflammation and DNA damage: cause, effect or both

Nature Reviews Rheumatology, Год журнала: 2023, Номер 19(4), С. 200 - 211

Опубликована: Фев. 7, 2023

Язык: Английский

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Therapeutics Targeting p53-MDM2 Interaction to Induce Cancer Cell Death

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 5005 - 5005

Опубликована: Апрель 30, 2022

Named as the guardian of genome, p53 is a tumor suppressor that regulates cell function, often through many different mechanisms such DNA repair, apoptosis, cycle arrest, senescence, metabolism, and autophagy. One genes activates MDM2, which forms negative feedback loop since MDM2 induces degradation p53. When activity inhibited, damaged cells do not undergo arrest or apoptosis. As 50% human cancers inactivate by mutation, current research focuses on reactivating developing drugs target p53-MDM2 interaction, includes binding phosphorylation The objective this article to provide short list description antagonists may be excellent candidates for inducing cancer death. Relevant articles were searched identified using online databases PubMed ScienceDirect. Increasing levels, targeting can help play its role induce Researchers have compounds act inhibitors, either directly modifying with phosphorylation. results associated demonstrate importance interactions inhibit growth, indicates use improve therapeutics.

Язык: Английский

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miRNA dysregulation is an emerging modulator of genomic instability

Seminars in Cancer Biology, Год журнала: 2021, Номер 76, С. 120 - 131

Опубликована: Май 9, 2021

Язык: Английский

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Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Янв. 12, 2021

Abstract Epstein–Barr virus-associated diseases are important global health concerns. As a group I carcinogen, EBV accounts for 1.5% of human malignances, including both epithelial- and lymphatic-originated tumors. Moreover, plays an etiological pathogenic role in number non-neoplastic diseases, is even involved multiple autoimmune (SADs). In this review, we summarize discuss some recent exciting discoveries research area, which DNA methylation alterations, metabolic reprogramming, the changes mitochondria ubiquitin-proteasome system (UPS), oxidative stress lytic reactivation, variations non-coding RNA (ncRNA), radiochemotherapy immunotherapy. Understanding learning from advancement will further confirm far-reaching future value therapeutic strategies EBV-associated diseases.

Язык: Английский

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Emerging role of PARP‐1 and PARthanatos in ischemic stroke

Journal of Neurochemistry, Год журнала: 2021, Номер 160(1), С. 74 - 87

Опубликована: Июль 9, 2021

Cell death is a key feature of neurological diseases, including stroke and neurodegenerative disorders. Studies in variety ischemic/hypoxic mouse models demonstrate that poly(ADP-ribose) polymerase 1 (PARP-1)-dependent cell death, also named PARthanatos, plays pivotal role ischemic neuronal disease progress. PARthanatos has its unique triggers, processors, executors convey highly orchestrated programmed signaling cascade. In addition to gene transcription, DNA damage repair, energy homeostasis through PARylation various targets, PARP-1 activation neuron glia attributes brain following ischemia/reperfusion. Pharmacological inhibition or genetic deletion reduces infarct volume, eliminates inflammation, improves recovery functions stroke. Here, we reviewed the their therapeutic potential.

Язык: Английский

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Combining targeted DNA repair inhibition and immune-oncology approaches for enhanced tumor control

Molecular Cell, Год журнала: 2023, Номер 83(5), С. 660 - 680

Опубликована: Янв. 19, 2023

Язык: Английский

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