Exploring oncology treatment strategies with tyrosine kinase inhibitors through advanced 3D models (Review) DOI Creative Commons
Giorgia Isinelli, S. Failla, Roberto Plebani

et al.

Medicine International, Journal Year: 2024, Volume and Issue: 5(2)

Published: Dec. 20, 2024

The limitations of two‑dimensional (2D) models in cancer research have hindered progress fully understanding the complexities drug resistance and therapeutic failures. However, three‑dimensional (3D) provide a more accurate representation in vivo environments, capturing critical cellular interactions dynamics that are essential evaluating efficacy toxicity tyrosine kinase inhibitors (TKIs). These advanced enable researchers to explore mechanisms with greater precision, optimizing treatment strategies improving predictive accuracy clinical outcomes. By leveraging 3D models, it will be possible deepen current TKIs drive forward innovations treatment. present review discusses 2D transformative impact on oncology research, highlighting their roles addressing challenges systems advancing TKI studies.

Language: Английский

Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities DOI Creative Commons
Muttiah Barathan, Sook Luan Ng, Yogeswaran Lokanathan

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(5), P. 654 - 654

Published: May 14, 2024

Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms devising effective therapeutic strategies. This review provides comprehensive overview the landscape extracellular vesicles (EVs) context breast highlighting their diverse subtypes, biogenesis, roles intercellular communication within tumour microenvironment (TME). The discussion spans various aspects, from EVs stromal cells cancer to influence on angiogenesis, immune response, chemoresistance. impact EV production different culture systems, including two dimensional (2D), three (3D), organoid models, is explored. Furthermore, this delves into potential presenting emerging strategies such as engineered for gene delivery, nanoplatforms targeted chemotherapy, disrupting derived treatment approach. Understanding these complex interactions milieu crucial identifying developing new targets.

Language: Английский

Citations

5
Patient-Derived Tumor Organoids: A Platform for Precision Therapy of Colorectal Cancer DOI Creative Commons
Yiran Li, Wei Wu, Jiaxin Yao

et al.

Cell Transplantation, Journal Year: 2025, Volume and Issue: 34

Published: Jan. 1, 2025

Colorectal cancer (CRC) represents a significant cause of cancer-related mortality on global scale. It is highly heterogeneous cancer, and the response patients to homogeneous drug therapy varies considerably. Patient-derived tumor organoids (PDTOs) represent an optimal preclinical model for research. A substantial body evidence from numerous studies has demonstrated that PDTOs can accurately predict patient’s different treatments. This article outlines utilization in management CRC across range therapeutic contexts, including postoperative adjuvant chemotherapy, palliative neoadjuvant chemoradiotherapy, targeted therapy, third-line follow-up treatment, treatment elderly patients. delineates manner which inform decisions at all stages CRC, thereby assisting clinicians selecting options reducing risk toxicity resistance associated with clinical drugs. Moreover, it identifies shortcomings existing PDTOs, absence consistent criteria assessing sensitivity tests, lack vascular microenvironment models, high cost technology. In conclusion, despite their inherent limitations, offer several advantages, rapid culture, success rate, consistency, throughput, be employed as personalized option CRC. The use allows prediction responses modalities various disease progression. potential reduce adverse reactions emergence drugs, facilitate evidence-based decision-making, guide selection medications, advancing individualized

Language: Английский

Citations

0
Cell culture techniques for cancer research DOI
Preeti Jain, N. V. Joshi, Sadhna Aggarwal

et al.

Methods in cell biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Citations

0
Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance DOI Creative Commons
Lanyue Zhang,

Jiangnan Zhao,

Changqing Su

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Metabolic reprogramming is a hallmark of ovarian cancer, enabling tumor progression, immune evasion and drug resistance. The microenvironment (TME) further shapes metabolic adaptations, cancer cells to withstand hypoxia nutrient deprivation. While organoid models provide physiologically relevant platform for studying these processes, they still lack vascular components, limiting their ability fully recapitulate metabolism responses. In this study, we investigated the key mechanisms involved in focusing on glycolysis, lipid amino acid metabolism. We integrated metabolomic analyses sensitivity assays explore metabolic-TME interactions using patient-derived, adult stem cell-derived iPSC-derived organ tissues. Among these, found that play central role progression chemotherapy identified methylglyoxal (MGO)-mediated BRCA2 dysfunction as driver escape, sphingolipid signaling proliferation kynurenine CD8+ T cell suppression. addition, PI3K/AKT/mTOR Wnt/β-catenin pathways promote chemoresistance through adaptation. By elucidating link between evasion, study identifies vulnerabilities potential targets cancer. Our findings support development metabolically targeted therapies increase utility organoid-based precision medicine models.

Language: Английский

Citations

0
Inducing Targeted, Caspase-Independent Apoptosis with New Chimeric Proteins for Treatment of Solid Cancers DOI Open Access

Orly Melloul,

Samar Zabit,

Michal Lichtenstein

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1179 - 1179

Published: March 31, 2025

Background: Most newly developed anticancer treatments trigger tumor cell death through apoptosis, for which involvement of caspases activity is essential. However, numerous mutations in apoptotic pathways that lead to cancer and favor resistance apoptosis are known; most related caspase-dependent thus have low efficacy. To overcome these limitations, we constructed a novel chimeric protein, GnRH-AIF, using gonadotropin-releasing hormone (GnRH) analog as targeting moiety the apoptosis-inducing factor (AIF) its cleaved form killing moiety, fused at cDNA level. AIF has crucial role caspase-independent pathway. A wide variety solid tumors overexpress GnRH-receptors (GnRH-R) targeted by new GnRH-AIF protein. Methods Results: In this study, constructed, expressed, highly purified proteins. We demonstrated ability chimera enter specifically very efficiently kill lines overexpressing GnRH-R. importantly, upon entry, GnRH-AIFs translocate nucleus where it causes DNA fragmentation leading direct death. As AIFs lack nuclease activity, our findings also emphasize induced dependent on presence ENDOG PPIA proteins, known participate formation DNA-degradosome complex. Finally, high anti-tumor efficacy ex vivo, human, colon organoid model. Conclusions: Our study shows potential protein approach treat cancers GnRH-R, via

Language: Английский

Citations

0
ULK1 promotes metastatic progression in epithelial ovarian cancer DOI
Trevor G. Shepherd, Jack C. Webb,

Adrian Buensuceso

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Epithelial ovarian cancer (EOC) is a leading cause of gynecological mortality, driven largely by late diagnosis and chemo-resistant disease. While autophagy plays critical role in the survival EOC spheroids during metastasis, ULK1, key regulator autophagy, progression remains unclear. To investigate this, we utilized CRISPR/Cas9 technology to delete ULK1 cell lines OVCAR8 HEYA8, immortalized fallopian tube epithelial line FT190. Immunoblotting confirmed loss its associated disruption spheroids, evidenced reduced Beclin-1 phosphorylation, impaired LC3 processing, p62 accumulation. Culture-based assays revealed that knockout decreased spheroid viability due increased apoptosis and, notably, matrix-bound organoid growth, offering new insights into potential ULK1 affecting tumor growth spread. These findings were further demonstrated in vivo xenograft models, which significantly burden metastatic potential. The for requirement properties was supported diminished invasive capacity cells mesothelial clearance assays. mechanisms contributes conducted proteomic analyses disrupted signaling pathways, including MEK-MAPK, PI3K-AKT-mTOR, regulation. Although failed synergize with standard-of-care chemotherapeutics, it enhanced sensitivity MEK mTOR inhibition, revealing therapeutic combinations target via MAPK PI3K-AKT-mTOR pathway vulnerabilities EOC. Overall, this study highlights as multiple steps underscoring novel advanced cancer.

Language: Английский

Citations

0
Advanced organoid models for targeting Kras-driven lung adenocarcinoma in drug discovery and combination therapy DOI Creative Commons
İsa Taş, Reinhilde Jacobs, Juliane Albrecht

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 24, 2025

Abstract Background Lung cancer remains one of the most challenging diseases to treat due its heterogeneity. Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutations are genetic drivers in numerous types including lung adenocarcinoma (LUAD). Despite recent advances KRAS-targeted therapies, treatment resistance and limited therapeutic options necessitate advanced preclinical models, such as organoids, identify personalized therapies by screening novel strategies synergistic drug combinations. Results We established LUAD genetically engineered mouse (GEM) models Kras G12V & Trp53 Δex2−10 (KP) KP with Ctnnb1 Δex3 mutation (KPC). Tumor-derived organoids from these recapitulated genomic landscape histopathological characteristics their parental tumors. The displayed tumorigenic potential when implanted immunocompromised mice, forming tumors contrast unlike healthy lung-derived organoids. Drug identified effective kinase inhibitors DNA methyltransferase (DNMT) against Notably, combination drugs exhibited highest synergy KPC Conclusion successfully developed harboring multiple agents targeting cells. Furthermore, we demonstrated effectiveness a DNMT inhibitor-based therapy, presenting promising strategy for this subtype.

Language: Английский

Citations

0
Interleukin 13 Promotes Maturation and Proliferation in Metaplastic Gastroids DOI Creative Commons

Ela W. Contreras-Panta,

Su-Hyung Lee,

Yoonkyung Won

et al.

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 18(3), P. 101366 - 101366

Published: Jan. 1, 2024

Type 2 innate lymphoid cells (ILC2s) and interleukin-13 (IL-13) promote the onset of spasmolytic polypeptide-expressing metaplasia (SPEM) cells. However, little is known about molecular effects IL-13 in SPEM We now sought to establish a reliable organoid model, Meta1 gastroids, model vitro. evaluated cellular ILC2s on maturation proliferation

Language: Английский

Citations

3
Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma DOI Creative Commons

Sirayot Areewong,

Orawan Suppramote,

Sunisa Prasopporn

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Nov. 5, 2024

Abstract Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead acquired resistance current treatments. However, recent evidence suggests that drug is associated with fitness cost resulting from the myriad of alterations under selective pressure primary treatment. Consequently, CCA patients are more susceptible alternative therapies ineffective as monotherapies. This phenomenon, termed “acquired vulnerability,” has garnered significant interest in development, could potentially be exploited therapeutically. review elucidates modes vulnerability, methods for identifying exploiting vulnerabilities cancer (particularly CCA), strategies enhance clinical efficacy combinations by leveraging principle vulnerability. Identifying may pave way novel effectively treat highly heterogeneous adaptable malignancies such CCA.

Language: Английский

Citations

2
Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy DOI
Meghan Logun, Xin Wang, Yusha Sun

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

2