Patient-derived xenograft models in cancer therapy: technologies and applications

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

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Circulating tumour cells for early detection of clinically relevant cancer

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(7), P. 487 - 500

Published: June 2, 2023

Language: Английский

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The Role of Circulating Tumor Cells as a Liquid Biopsy for Cancer: Advances, Biology, Technical Challenges, and Clinical Relevance

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1377 - 1377

Published: March 31, 2024

Cancer remains a leading cause of mortality worldwide, with metastasis significantly contributing to its lethality. The metastatic spread tumor cells, primarily through the bloodstream, underscores importance circulating cells (CTCs) in oncological research. As critical component liquid biopsies, CTCs offer non-invasive and dynamic window into biology, providing invaluable insights cancer dissemination, disease progression, response treatment. This review article delves recent advancements CTC research, highlighting their emerging role as biomarker various types. We explore latest technologies methods for isolation detection, alongside novel approaches characterizing biology genomics, transcriptomics, proteomics, epigenetic profiling. Additionally, we examine clinical implementation these findings, assessing how are transforming landscape diagnosis, prognosis, management. By offering comprehensive overview current developments potential future directions, this significance enhancing our understanding shaping personalized therapeutic strategies, particularly patients disease.

Language: Английский

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Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1–HER3 signaling

Nature Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance circulation, robust CTC expansion protocols are urgently needed effectively study disease progression and therapy responses. Here we present establishment long-term CTC-derived organoids from female metastatic Multiomics analysis along preclinical modeling xenografts identified neuregulin 1 (NRG1)–ERBB2 receptor tyrosine kinase 3 ( ERBB3 /HER3) signaling as a key pathway required for survival, growth dissemination. Genome-wide CRISPR activation screens revealed that fibroblast factor (FGFR1) serves compensatory function NRG1–HER3 axis rescues NRG1 deficiency CTCs. Conversely, induced resistance FGFR1 inhibition, whereas combinatorial blockade impaired growth. The dynamic interplay between reveals molecular basis cancer cell plasticity clinically relevant strategies target it. Our organoid platform enables identification validation patient-specific vulnerabilities represents an innovative tool precision medicine.

Language: Английский

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Crucial roles of circulating tumor cells in the metastatic cascade and tumor immune escape: biology and clinical translation

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(12), P. e005615 - e005615

Published: Dec. 1, 2022

Cancer-related deaths are mainly caused by metastatic spread of tumor cells from the primary lesion to distant sites via blood circulation. Understanding mechanisms blood-borne cell dissemination detection and molecular characterization circulating (CTCs) in patients with cancer has opened a new avenue research. Recent technical advances have enabled comprehensive analysis CTCs at genome, transcriptome protein level as well first functional studies using patient-derived CTC lines. In this review, we describe discuss how research on yielded important insights into biology metastasis response therapies directed against cells. Future investigations will show whether leaving their site more vulnerable attacks immune effector might be 'Achilles heel' progression. Here, focus lessons learned particular emphasis interactions system. Moreover, briefly potential challenges for implementing clinical decision-making including minimal residual disease, monitoring efficacies systemic identification therapeutic targets resistance mechanisms.

Language: Английский

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Preclinical models for drug discovery for metastatic disease

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1792 - 1813

Published: April 1, 2023

Language: Английский

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Enhancing clinical potential of liquid biopsy through a multi-omic approach: A systematic review

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: April 3, 2023

In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative replicable over time. This revolutionary approach can be complementary may, in future, replace tissue biopsy, which is still considered gold standard diagnosis. "Classical" often cannot provide sufficient bioptic material advanced screening, isolated information about disease evolution heterogeneity. Recent literature highlighted how of proteomic, genomic, epigenetic, metabolic alterations. These biomarkers detected investigated using single-omic and, recently, combination through multi-omic approaches. review will an overview most suitable techniques to thoroughly characterize tumor their potential applications, highlighting importance integrated multi-omic, multi-analyte approach. Personalized medical investigations soon allow patients receive predictable prognostic evaluations, early diagnosis, subsequent

Language: Английский

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ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 22, 2023

Metastases are the major cause of cancer-related morbidity and mortality. By time cancer cells detach from their primary site to eventually spread distant sites, they need acquire ability survive in non-adherent conditions proliferate within a new microenvironment spite stressing that may severely constrain metastatic process. In this study, we gained insight into molecular mechanisms allowing an anchorage-independent manner, regardless both tumor-intrinsic variables nutrient culture conditions.3D spheroids derived lung adenocarcinoma (LUAD) breast were cultured either nutrient-rich or -restricted conditions. A multi-omics approach, including transcriptomics, proteomics, metabolomics, was used explore changes underlying transition 2 3D cultures. Small interfering RNA-mediated loss function assays validate role identified differentially expressed genes proteins H460 HCC827 LUAD as well MCF7 T47D cell lines.We found cultures is associated with significant expression involved metabolic reprogramming. particular, observed tumor spheroid growth implies overexpression ALDOC ENO2 glycolytic enzymes concomitant enhanced consumption glucose fructose production lactate. Transfection siRNA against determined reduction lactate production, viability size produced by H460, HCC827, MCF7, lines.Our results show survival supported drive metabolism towards production. Notably, finding valid for all lines have analyzed different environmental broader Validation mechanism other origin will be necessary broaden types. Future vivo studies assess metastasis.

Language: Английский

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Clinical applications of circulating tumor cells in patients with solid tumors

Clinical & Experimental Metastasis, Journal Year: 2024, Volume and Issue: 41(4), P. 403 - 411

Published: Jan. 28, 2024

Abstract The concept of liquid biopsy analysis has been established more than a decade ago. Since the establishment term, tremendous advances have achieved and plenty methods as well analytes investigated in basic research clinical trials. Liquid refers to body fluid-based that is minimal-invasive, most importantly, allows dense monitoring tumor responses by sequential blood sampling. Blood important analyte for analyses, providing an easily accessible source plethora cells, cell-derived products, free nucleic acids, proteins vesicles. More 12,000 publications are listed PubMed today including term biopsy. In this manuscript, we critically review current implications biopsy, with special focus on circulating describe hurdles need be addressed before can implemented standard care guidelines.

Language: Английский

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Liquid Biopsy in the Clinical Management of Cancers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8594 - 8594

Published: Aug. 6, 2024

Liquid biopsy, a noninvasive diagnosis that examines circulating tumor components in body fluids, is increasingly used cancer management. An overview of relevant literature emphasizes the current state liquid biopsy applications care. Biomarkers particularly DNA (ctDNA), RNAs (ctRNA), cells (CTCs), extracellular vesicles (EVs), and other components, offer promising opportunities for early diagnosis, treatment selection, monitoring, disease assessment. The implementation precision medicine has shown significant potential various types, including lung cancer, colorectal breast prostate cancer. Advances genomic molecular technologies such as next-generation sequencing (NGS) digital polymerase chain reaction (dPCR) have expanded utility enabling detection somatic variants actionable alterations tumors. also demonstrated predicting responses, monitoring minimal residual (MRD), assessing heterogeneity. Nevertheless, standardizing techniques, interpreting results, integrating them into clinical routine remain challenges. Despite these challenges, implications management, offering dynamic approach to understanding biology guiding personalized strategies.

Language: Английский

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