Radiation Sensitivity: The Rise of Predictive Patient-Derived Cancer Models DOI

Liliana L Berube,

Kwangok P. Nickel, Mari Iida

et al.

Seminars in Radiation Oncology, Journal Year: 2023, Volume and Issue: 33(3), P. 279 - 286

Published: June 16, 2023

Language: Английский

Patient-derived xenograft models in cancer therapy: technologies and applications DOI Creative Commons
Yihan Liu,

Wantao Wu,

Changjing Cai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 12, 2023

Abstract Patient-derived xenograft (PDX) models, in which tumor tissues from patients are implanted into immunocompromised or humanized mice, have shown superiority recapitulating the characteristics of cancer, such as spatial structure cancer and intratumor heterogeneity cancer. Moreover, PDX models retain genomic features across different stages, subtypes, diversified treatment backgrounds. Optimized engraftment procedures modern technologies multi-omics deep learning enabled a more comprehensive depiction molecular landscape boosted utilization models. These irreplaceable advantages make an ideal choice studies, preclinical trials novel drugs, validating drug combinations, screening drug-sensitive patients, exploring resistance mechanisms. In this review, we gave overview history process model establishment. Subsequently, review presents strengths weaknesses highlights integration research. Finally, delineated broad application chemotherapy, targeted therapy, immunotherapy, other therapies.

Language: Английский

Citations

178

Patient‐derived xenograft model in cancer: establishment and applications DOI Creative Commons

Ao Gu,

Jiatong Li, Mengyao Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 19, 2025

Abstract The patient‐derived xenograft (PDX) model is a crucial in vivo extensively employed cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, diverse treatment histories. Various strategies utilized PDX models can offer valuable insights into mechanisms tumor progression, drug resistance, development novel therapies. This review provides comprehensive overview establishment applications models. We present an history current status models, elucidate construction methodologies for different tumors, conduct comparative analysis highlight distinct advantages limitations this relation other are elucidated domain comprehending underlying therapy, which highlights broad fields chemotherapy, targeted delivery systems, combination antibody–drug conjugates radiotherapy. Furthermore, with multiomics single‐cell analyses also emphasized. application clinical personalized medicine additionally

Language: Английский

Citations

5

Inhibition of platin-induced BCL2 increase overcomes chemoresistance in squamous cell carcinoma of the head and neck through resensitization to cell death DOI Creative Commons
Anne‐Sophie Becker,

Friederike Klauk,

Thomas Freitag

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102308 - 102308

Published: Feb. 18, 2025

Language: Английский

Citations

0

Advancements in CRISPR screens for the development of cancer immunotherapy strategies DOI Creative Commons
Yan-Ruide Li,

Zibai Lyu,

Yanxin Tian

et al.

Molecular Therapy — Oncolytics, Journal Year: 2023, Volume and Issue: 31, P. 100733 - 100733

Published: Oct. 5, 2023

CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb expression. In field cancer immunotherapy, this has empowered discovery genes, biomarkers, pathways that regulate tumor development progression, immune reactivity, effectiveness immunotherapeutic interventions. By conducting large-scale genetic screens, researchers have successfully identified novel targets impede growth, enhance anti-tumor responses, surmount immunosuppression within microenvironment (TME). Here, we present an overview screens conducted in cells for purpose identifying therapeutic targets. We also explore application propel advancement cell-based therapies, encompassing T cells, natural killer dendritic macrophages. Furthermore, outline crucial components necessary successful implementation immune-specific potential directions future research.

Language: Английский

Citations

9

Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma DOI Creative Commons

Maureen Jacob,

Sara Wiedemann,

Daniela Brücher

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(10), P. 1667 - 1678

Published: Sept. 19, 2023

Abstract Background Neuroblastoma is a paediatric cancer that characterised by poor prognosis for chemoresistant disease, highlighting the need better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate neuroblastoma cells. Methods We utilised cisplatin-adapted cell lines as well patient tissues before and after relapse to study alterations of upon chemoresistance. Results In direct comparison cisplatin-resistant cells identified prominent loss sensitivity BCL2/BCL-X L inhibitors associated with an increase in MCL1 dependency high expression tumour tissues. Screening FDA-approved anti-cancer drugs therapeutics be beneficial combination clinically tested BH3-mimetic ABT263, but no synergistic drug interactions selective inhibitor S63845. Further exploration potential options immunotherapy based on NK highly promising, since are able efficiently kill both parental Conclusions These data highlight application differ between first line relapsed disease. Combination cell-based further killing neuroblastoma, outlining new strategy neuroblastoma.

Language: Английский

Citations

6

Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia DOI Creative Commons
Han Wang, Huiying Sun,

Bilin Liang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 25, 2023

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, molecular mechanism relapse remains unclear. To fill this gap in knowledge, here we characterize chromatin accessibility landscape relapsed B-ALL. We observe rewired accessible regions (ACRs) associated with transcription dysregulation cells as compared normal B-cell progenitors. show that over a quarter ACRs B-ALL are quiescent high heterogeneity among B-ALLs. identify subtype-specific and allele-imbalanced by integrating multi-omics data. By characterizing differential between diagnosis B-ALL, alterations during drug treatment. Further analysis free survival leads to identification subgroup which early relapse. These data provide an advanced integrative portrait importance tumorigenesis responses.

Language: Английский

Citations

5

Developing pioneering pharmacological strategies with CRISPR/Cas9 library screening to overcome cancer drug resistance DOI

Yu He,

Huan Li,

Xueming Ju

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189212 - 189212

Published: Nov. 1, 2024

Language: Английский

Citations

0

Nodularin‐R Synergistically Enhances Abiraterone Against Castrate‐ Resistant Prostate Cancer via PPP1CA Inhibition DOI Creative Commons
Yao Huang, Yi Cen,

Hualing Wu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(22)

Published: Nov. 1, 2024

ABSTRACT Clinically, most prostate cancer (PCa) patients inevitably progress to castration‐resistant (CRPC) with poor prognosis after androgen deprivation therapy (ADT), including abiraterone, the drug of choice for ADT. Therefore, it is necessary explore resistance mechanism abiraterone in depth. Genome‐wide CRISPR/Cas9 knockout technology was used screen CRPC cell line 22Rv1 abiraterone‐resistant genes. Combined bioinformatics, a key gene high expression and screened. Then, effects target on function were explored by silencing overexpression. Further, natural product potential targeting effect identified validated molecular docking protein expression. Molecular dynamics simulations revealed affecting Finally, combined anti‐CRPC cellular vivo experiments. Five common genes (KCNJ3, COL2A1, PPP1CA, MDH2 EXOSC5) successfully, among which PPP1CA had worst disease‐free survival. Moreover, highly expressed cells. Silencing increased sensitivity while promoting apoptosis inhibiting clone formation. Overexpressing exerted opposite effects. binding mode nodularin‐R dose‐dependent manner inhibition. Mechanistically, attenuates interaction between USP11 (deubiquitinating enzyme), potentially degradation. Additionally, combination 2.72 μM 54.5 synergistically inhibited resistant function. In experiments also that significantly tumour growth reduced inducible PPP1CA. driver resistance, enhances

Language: Английский

Citations

0

New Agents DOI
Francisco Bautista, C. Michel Zwaan,

Andrej Lissat

et al.

Pediatric oncology, Journal Year: 2024, Volume and Issue: unknown, P. 373 - 397

Published: Jan. 1, 2024

Citations

0

Radiation Sensitivity: The Rise of Predictive Patient-Derived Cancer Models DOI

Liliana L Berube,

Kwangok P. Nickel, Mari Iida

et al.

Seminars in Radiation Oncology, Journal Year: 2023, Volume and Issue: 33(3), P. 279 - 286

Published: June 16, 2023

Language: Английский

Citations

0