CRISPR based therapeutics: a new paradigm in cancer precision medicine

Das, Sumit; Bano, Shehnaz; Kapse, Prachi; Kundu, Gopal C.

doi:10.1186/s12943-022-01552-6

Cited by 22 publications

(18 citation statements)

References 126 publications

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“…At the same time the benefits of Precision/Personalized Medicine and the major obstacles for all stakeholders involved are summarized as well as specific solutions are provided. Knowledge and perception of Medical and Pharmacy students towards Pharmacogenomics and Genetics is also presented [6, 8–10, 22, 27–29, 33, 34, 45, 51, 53–55, 59, 67, 74–77, 81–83, 85–107, 112, 113, 121].…”

Section: Resultsmentioning

confidence: 99%

Advancing precision medicine in medical education: Integrated, precise and data‐driven smart solutions

Papadopoulou

Lytras

2023

Applied Research

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Advances in “Precision Medicine” initiative, also known as “Personalized Medicine” is an emerging approach for disease treatment and prevention that has already led to innovative discoveries and has created “smart” applications and solutions tailored to a person's or a group of individuals' genetic profile, lifestyle, and environment interaction. Already many physicians as part of patient care routinely prescribe various molecular/genetic and other tests enabling them to select personalized treatments that improve the chances of survival and reduce exposure to adverse effects. This initiative should provide to medical and healthcare professionals with adequate resources and readily available solutions so that the target to specific treatments and care of the illnesses is achieved while at the same time protecting the privacy and safety of the individual is secured as well as the Electronic Health Records (EHRs) and whatever additional data is necessary within the context of Precision Medicine. This study, through a literature review mostly, and some case study analysis, examine whether personalized medicine is delivered to the patient in an “accurate” and “precise” way, as expected. This requires that Health and Human Services and other stakeholders and agencies collaborate to solicit the right input from patients while at the same time can identify and address any educational, practical, legal, and technical issues and providing smart solutions. The lack of proper medical education and advanced infrastructure are still major barriers to the adoption of Precision Medicine, therefore, the role of medical training in Precision Medicine is also examined and analyzed. Specific examples are discussed in an integrated, precise, and data‐driven manner to provide “smart” solutions.

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Section: Resultsmentioning

confidence: 99%

Advancing precision medicine in medical education: Integrated, precise and data‐driven smart solutions

Papadopoulou

Lytras

2023

Applied Research

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“…Research on gene silencing is progressing with the application of CRISPR interference, which physically inhibits the transcription process without altering the DNA sequence 48 . While various viral and non‐viral vectors that can carry CRISPR‐Cas components to different target organs are under development and are expected to contribute to individualization of cancer precision medicine, 49 enhancer regions of the ITPR3 gene might be targeted by these techniques.…”

Section: Discussionmentioning

confidence: 99%

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Mima

Okabe

Hoshii

et al. 2023

Intl Journal of Cancer

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Human papillomavirus (HPV) is causally involved in the development of head and neck squamous cell carcinoma (HNSCC). The integration of HPV drives tumorigenesis through expression of oncogenic viral genes as well as genomic alterations in surrounding regions. To elucidate involvement of epigenetic dysregulation in tumorigenesis, we here performed integrated analyses of the epigenome, transcriptome and interactome using ChIP‐seq, RNA‐seq and Hi‐C and 4C‐seq for HPV(+) HNSCCs. We analyzed clinical HNSCC using The Cancer Genome Atlas data and found that genes neighboring HPV integration sites were significantly upregulated and were correlated with oncogenic phenotypes in HPV(+) HNSCCs. While we found four HPV integration sites in HPV(+) HNSCC cell line UPCI‐SCC‐090 through target enrichment sequencing, 4C‐seq revealed 0.5 to 40 Mb of HPV‐interacting regions (HPVIRs) where host genomic regions interacted with integrated HPV genomes. While 9% of the HPVIRs were amplified and activated epigenetically forming super‐enhancers, the remaining non‐amplified regions were found to show a significant increase in H3K27ac levels and an upregulation of genes associated with GO terms, for example, Signaling by WNT and Cell Cycle. Among those genes, ITPR3 was significantly upregulated, involving UPCI‐SCC‐090‐specific super‐enhancer formation around the ITPR3 promoter and in the 80‐kb‐downstream region. The knockdown of ITPR3 by siRNA or CRISPR deletions of the distant enhancer region led to a significant suppression of cell proliferation. The epigenetic activation of HPVIRs was also confirmed in other cell lines, UM‐SCC‐47 and UM‐SCC‐104. These data indicate that epigenetic activation in HPVIRs contributes, at least partially, to genesis of HPV(+) HNSCC.

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“…However, features of transcription factor interactions with DNA and co-factors—elements of disorder or ‘fuzziness’ without structured binding pockets [ 24 , 25 ]—limited progress in the field for decades, and there was a general consensus that transcription was undruggable. Recent developments that promise to reverse this perspective include new knowledge of intrinsically disordered proteins, cellular thermal shift assays to interrogate target engagement, binding-focused drug screening methodologies, proteolysis targeting chimera-based therapeutics, and CRISPR-directed transcriptional interventions [ 26 , 27 ]. In the area of medical oncology in particular, numerous therapeutics that target transcription factor activity are currently under development or have already entered clinical trials [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding

Ashander

Appukuttan

et al. 2023

IJMS

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The interaction between leukocytes and cytokine-activated retinal endothelium is an initiating step in non-infectious uveitis involving the posterior eye, mediated by cell adhesion molecules. However, because cell adhesion molecules are required for immune surveillance, therapeutic interventions would ideally be employed indirectly. Using 28 primary human retinal endothelial cell isolates, this study sought to identify transcription factor targets for reducing levels of the key retinal endothelial cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, and limiting leukocyte binding to the retinal endothelium. Five candidate transcription factors – C2CD4B, EGR3, FOSB, IRF1, and JUNB – were identified by differential expression analysis of a transcriptome generated from IL-1β- or TNF-α-stimulated human retinal endothelial cells, interpreted in the context of the published literature. Further filtering involved molecular studies: of the five candidates, C2CD4B and IRF1 consistently demonstrated extended induction in IL-1β- or TNF-α-activated retinal endothelial cells and demonstrated a significant decrease in both ICAM-1 transcript and ICAM-1 membrane-bound protein expression by cytokine-activated retinal endothelial cells following treatment with small interfering RNA. RNA interference of C2CD4B or IRF1 significantly reduced leukocyte binding in a majority of human retinal endothelial cell isolates stimulated by IL-1β or TNF-α. Our observations suggest that the transcription factors C2CD4B and IRF1 may be potential drug targets for limiting leukocyte–retinal endothelial cell interactions in non-infectious uveitis involving the posterior eye.

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CRISPR based therapeutics: a new paradigm in cancer precision medicine

Cited by 22 publications

References 126 publications

Advancing precision medicine in medical education: Integrated, precise and data‐driven smart solutions

Advancing precision medicine in medical education: Integrated, precise and data‐driven smart solutions

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding

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