Interplay between the DNA Damage Response and Immunotherapy Response in Cancer

Lee, Elizabeth Chun Yong; Kok, Jessica Sook Ting; Teh, Bin Tean; Lim, Kah Suan

doi:10.3390/ijms232113356

Cited by 5 publications

(3 citation statements)

References 193 publications

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“…Immuno evasion subsequently stops the host immune system from identifying these transformed cells. Cancer has proven to respond well to treatments that target immune evasion and genetic instability ( Lee et al, 2022 ). Variations in DNA damage response genes and the resultant genomic instability have a significant role in determining the antigenicity of tumors via both neoantigen-dependent and independent processes ( Li and Chen, 2018 ).…”

Section: Advancement In Synergy Between Ddr and Itmentioning

confidence: 99%

The future of cancer treatment: combining radiotherapy with immunotherapy

Dagar,

Gupta,

Shankar

et al. 2024

Front. Mol. Biosci.

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Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other’s beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell’s genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy.

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Section: Advancement In Synergy Between Ddr and Itmentioning

confidence: 99%

The future of cancer treatment: combining radiotherapy with immunotherapy

Dagar,

Gupta,

Shankar

et al. 2024

Front. Mol. Biosci.

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“…Immune-mediated mechanisms of tumor development may have some relevance to BRCA1-driven neoplasms, as BRCA1 inactivation is accompanied by the de ciency in homologous DNA repair and, consequently, chromosomal instability. Several studies revealed increased tumor antigenicity for BRCA1-associated hereditary cancers [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

HLA gene polymorphism is a modifier of age-related breast cancer penetrance in carriers of BRCA1 pathogenic alleles

Kuligina,

Romanko,

Jankevic

et al. 2024

Preprint

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Purpose Female carriers of germline BRCA1 mutations almost invariably develop breast cancer (BC) however the age at onset is a subject of variation. We hypothesized that the age-related penetrance of BRCA1 mutations may depend on inherited variability in the host immune system. Methods Next-generation sequencing was utilized for genotyping of HLA class I/II genes (HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1 and HLA-DRB1/3/4/5) in patients with BRCA1-associated BC with early (</= 38 years, n = 215) and late (>/= 58 years, n = 108) age at onset. Results HLA-DQB1*06:03P prevalence was higher in the late-onset group due to the excess of allele carriers [25/108 (23.1%) vs. 22/215 (10.2%); OR 2.96, p < 0.001]. For all HLA-I loci, there was a trend towards an increase in the number of homozygotes in the early-onset group. This trend reached statistical significance for the HLA-A [14.4% vs. 6.5%, p = 0.037; OR 2.4, p = 0.042]. The frequencies of HLA-DPB1, HLA-DQB1 and HLA-DRB1/3/4/5 homozygous genotypes did not differ between young-onset and late-onset patients. The maximum degree of homozygosity detected in this study was 6 out of 7 HLA class I/II loci; all six carriers of these genotypes were diagnosed with BC at the age </= 38 years [OR = 6.97, p = 0.187]. Conclusion HLA polymorphism may play a role in modifying the penetrance of BRCA1 pathogenic variants. Certain HLA alleles or HLA homozygosity may modify the risk of BC in BRCA1 carriers.

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“…It may be mediated by protooncogenes which control various biological processes in normal cells, serving as growth factors, transducers of cellular signals, and nuclear transcription factors [ 6 ]. In mammalian genomes, protooncogenes control normal cell differentiation and proliferation [ 7 ]. Any alterations to these genes that influence the structure of their encoded proteins may result in the development of oncogenes in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets

Pospieszna,

Dams-Kozlowska,

Udomsak

et al. 2023

IJMS

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Cancer remains a leading cause of death globally, and its complexity poses a significant challenge to effective treatment. Cancer stem cells and their markers have become key players in tumor growth and progression. CD133, a marker in various cancer types, is an active research area as a potential therapeutic target. This article explores the role of CD133 in cancer treatment, beginning with an overview of cancer statistics and an explanation of cancer stem cells and their markers. The rise of CD133 is discussed, including its structure, functions, and occurrence in different cancer types. Furthermore, the article covers CD133 as a therapeutic target, focusing on gene therapy, immunotherapy, and approaches to affect CD133 expression. Nanoparticles such as gold nanoparticles and nanoliposomes are also discussed in the context of CD133-targeted therapy. In conclusion, CD133 is a promising therapeutic target for cancer treatment. As research in this area progresses, it is hoped that CD133-targeted therapies will offer new and effective treatment options for cancer patients in the future.

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Interplay between the DNA Damage Response and Immunotherapy Response in Cancer

Cited by 5 publications

References 193 publications

The future of cancer treatment: combining radiotherapy with immunotherapy

The future of cancer treatment: combining radiotherapy with immunotherapy

HLA gene polymorphism is a modifier of age-related breast cancer penetrance in carriers of BRCA1 pathogenic alleles

Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets

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