Comparative analysis of 3D-culture techniques for multicellular colorectal tumour spheroids and development of a novel SW48 3D model DOI Creative Commons
Sergio Alonso,

Carlos Mateos-Sánchez,

Beatríz González

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Background Colorectal cancer (CRC) remains a significant global health challenge, with nearly 2 million diagnosed cases and over 900,000 deaths annually despite therapeutic advancements. The high morbidity mortality rates underscore the need for more efficient therapies. Three-dimensional (3D) cell culture models have emerged as physiologically relevant alternatives to traditional two-dimensional (2D) drug screening mechanistic studies. However, generating consistent spheroids across different CRC lines presents technical challenges, protocols remain inconsistent. Methods This study evaluated 3D methodologies, i.e. overlay on agarose, hanging drop, U-bottom plates without matrix or methylcellulose, Matrigel collagen type I hydrogels, eight lines. Tumorsphere morphology viability were analysed. Co-cultures immortalised colonic fibroblasts explored improve physiological relevance of tumour models. Results provided insights into morphological characteristics cultures multiple A novel compact spheroid model using SW48 line was successfully developed. Co-culture experiments offered additional tumour-stroma interactions in setting. Conclusions contributes advancement vitro models, potentially enhancing accuracy preclinical studies processes. successful expands repertoire available These findings may lead improved research development.

Language: Английский

Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance DOI Open Access
Samuele Tardito,

Serena Matis,

Maria Raffaella Zocchi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7131 - 7131

Published: June 28, 2024

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Therefore, need for new therapeutic strategies still a challenge. Surgery and chemotherapy represent first-line interventions; nevertheless, prognosis metastatic CRC (mCRC) patients remains unacceptable. An important step towards targeted therapy came from inhibition epidermal growth factor receptor (EGFR) pathway, by anti-EGFR antibody, Cetuximab, or specific tyrosine kinase inhibitors (TKI). mouse-human chimeric monoclonal antibody (mAb), binds to extracellular domain EGFR thus impairing EGFR-mediated signaling reducing cell proliferation. TKI can affect biochemical pathway at different steps along cascade. Apart other mAbs have been developed, such as Panitumumab. Both antibodies approved treatment KRAS-NRAS wild type mCRC, alone in combination with chemotherapy. These display strong differences activating host immune system against CRC, due their immunoglobulin isotypes. Although are efficient, drug resistance occurs high frequency. Resistant tumor populations either already be present before develop later adaptations genomic mutations pathway. Numerous efforts made improve efficacy find agents that able block downstream cascade molecules. Indeed, we examined importance analyzing antibody-drug conjugates (ADC) developed overcome and/or stimulate host's immunity growth. Also, patient-derived organoid cultures useful feasible vitro model study behavior response. Organoids reflect genetic heterogeneity found tissue origin, representing unique tool personalized medicine. Thus, CRC-derived smart studying microenvironment preclinical assay drugs.

Language: Английский

Citations

4
Molecular mechanism of angiogenesis in colorectal cancer DOI Creative Commons

Portia Raphela-Choma,

Mpho Choene, Lesetja R. Motadi

et al.

Gene Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102163 - 102163

Published: Feb. 1, 2025

Language: Английский

Citations

0
Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer DOI Open Access

Jennifer Haynes,

Prasath Manogaran

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1988 - 1988

Published: Feb. 25, 2025

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, with significant impact on public health. Current treatment options include surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy. Despite advancements in these therapeutic modalities, resistance remains challenge, often leading to failure, poor progression-free survival, recurrence. Mechanisms CRC are multifaceted, involving genetic mutations, epigenetic alterations, tumor heterogeneity, the microenvironment. Understanding mechanisms at molecular level crucial for identifying novel targets developing strategies overcome resistance. This review provides an overview diverse driving drug sporadic discusses currently under investigation counteract this Several promising being explored, including targeting transport, key signaling pathways, DNA damage response, cell death modifications, stem cells, The integration emerging approaches that target aims enhance efficacy current treatments improve patient outcomes.

Language: Английский

Citations

0
Utility of comprehensive genomic profiling combined with machine learning for prognostic stratification in stage II/III colorectal cancer after adjuvant chemotherapy DOI
Yosuke Kobayashi, Yoshiyuki Suzuki,

Ryo Seishima

et al.

International Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Sijunzi decoction granules for the treatment of advanced refractory colorectal cancer: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial DOI Creative Commons

Shuchang Nie,

Yu‐Wen Su, Lu Lu

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 20, 2025

Background Colorectal cancer (CRC) ranks among the most common gastrointestinal cancers globally, with both its incidence and mortality rates showing an upward trend. In particular, 5-year survival rate for stage IV CRC patients is only 14%. Conventional treatments such as chemotherapy immunotherapy can lead to drug resistance, exacerbate function damage, induce immunosuppression. Sijunzi decoction (SJZD), a fundamental formula of Traditional Chinese medicine (TCM), has been demonstrated confer distinct advantages in treatment CRC. Therefore, we designed this trial explore efficacy SJZD advanced refractory Methods A multicenter, randomized, double-blind, placebo-controlled being conducted assess effectiveness combined standard therapy treating Patients will be recruited randomly allocated either group or placebo 1:1 ratio. Both groups receive treatment. The intervention period last 6 months, follow-up assessments every 8 10 weeks. Progression-free (PFS) main outcome measure. And secondary outcomes contain duration disease control (DDC), overall (OS), completion chemotherapy, treatment-related adverse events, quality scale score tumor changes spleen deficiency patient-reported (PRO) scores following intervention. Expected To best our knowledge, marks first clinical investigation into therapeutic potential managing primary aim study provide robust evidence support integration TCM Western Trial registration was registered at Clinical Registry, http://www.chictr.org.cn (Registration No: ChiCTR2200065434); Date: 2022-11-04.

Language: Английский

Citations

0
Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 DOI Creative Commons
Ming Chen, Huiheng Qu, Xiao Liang

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 7, 2025

The incidence and mortality rates of colorectal cancer (CRC) are rising, it is the second most common cause cancer-related deaths worldwide. Although transcription factor, Brachyury intricately linked with various clinical malignancies, mechanisms by which influences CRC cell proliferation migration inadequately understood. Tissue microarray was used to evaluate expression in adjacent normal tissues. effects on HCT116 SW480 cells were also examined vitro, including using Cell Counting Kit-8, colony formation, transwell assays, vivo through subcutaneous tumorigenesis assays a nude mouse xenograft model. Chromatin immunoprecipitation binding MMP14 promoter its impact expression. Rescue experiments elucidate MMP14's role mediating Brachyury's effect behavior. significantly higher tissues than tissues, promotes oncogenesis vitro vivo. established as direct, downstream target, affirming that enhanced Brachyury-driven proliferation. Our findings highlight targeting Brachyury-MMP14 axis potential novel approach for therapy.

Language: Английский

Citations

0
Enhanced Therapeutic Efficacy of the Nanoscale Fluoropyrimidine Polymer CF10 in a Rat Colorectal Cancer Liver Metastasis Model DOI Open Access

Charles Chidi Okechukwu,

Xue Ma, Naresh Sah

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1360 - 1360

Published: March 30, 2024

Combination chemotherapy regimens that include fluoropyrimidine (FP) drugs, e.g., 5-fluorouracil (5-FU), are central to the treatment of colorectal cancer liver metastases (CRLMs), a major cause mortality. We tested second-generation FP polymer, CF10, in CC531/WAGRij syngeneic orthotopic rat model metastasis determine if CF10 improved response relative 5-FU. displayed increased potency 5-FU CC531 cells based on clonogenic assay results and caused apoptosis, as shown using live/dead assay. The was associated with replication stress, assessed by Western blot for biomarkers ATR/Chk1 ATM/Chk2 pathway activation. dosed deliver equivalent content an established dose rats (50 mg/kg) did not weight loss WAGRij even when combined ethynyl uracil (EU), inhibitor dihydropyrimidine dehydrogenase, enzyme primarily responsible degradation liver. In contrast, significant exacerbated combination EU. Importantly, significantly more effective than at inhibiting tumor progression (~90% reduction) CC531/WAG/Rij CRLM model. Our reveal strong potential be used treatment.

Language: Английский

Citations

3
Colorectal Cancer Screening and Management in Low- and Middle-Income Countries and High-Income Countries: A Narrative Review DOI Open Access

Barbara A Abreu Lopez,

Rafael Pinto-Colmenarez,

Fides Myles C. Caliwag

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Colorectal cancer (CRC) remains a leading global health challenge, being highly prevalent and major cause of cancer-related deaths worldwide. The incidence CRC varies significantly between high-income countries (HICs) low- middle-income (LMICs), with higher rates but lower mortality in HICs. Factors such as genetic predisposition, lifestyle, dietary habits play significant roles development, the Western diet limited access to screening contributing increased incidence. This review highlights disparities screening, management, outcomes HICs LMICs, benefiting from advanced methods like colonoscopy sigmoidoscopy, while LMICs face challenges due healthcare infrastructure resources. Tailored strategies, including low-cost options community-based initiatives, are critical improve early detection outcomes. Future directions for improving care globally include telemedicine, artificial intelligence, mobile technologies bridge gaps, well personalized medicine enhance treatment efficacy. Global collaboration investment necessary reduce CRC-related mortality, particularly resource-limited settings.

Language: Английский

Citations

3
Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer DOI Creative Commons
Aliye Ezgi Güleç Taşkıran, Diren Arda Karaoğlu, Cemil Can Eylem

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 48, P. 102078 - 102078

Published: Aug. 7, 2024

Glutamine is a non-essential amino acid that critical for cell growth. However, the differential metabolism of l-glutamine in metastatic versus primary colorectal cancer (CRC) has not been evaluated adequately.

Language: Английский

Citations

2
Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs DOI Creative Commons
Santu Sarkar, Sezgin Kiren, William H. Gmeiner

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 734 - 734

Published: May 29, 2024

Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment colorectal cancer (CRC). FP-based has improved survival outcomes over last several decades with much therapeutic benefit derived from optimization dose and delivery. To provide further advances in efficacy, next-generation prodrugs nanodelivery systems FPs being developed. This review focuses on recent innovative approaches FP that display promise. We summarize established, clinically useful prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression optimal anticancer activity. then describe use DNA-based polymers (e.g., CF10) delivery activated nucleotides as a approach proven activity pre-clinical models clinical potential. Multiple show promise CRC we albumin-mediated delivery, development mesoporous silica nanoparticles, emulsion-based metal hydrogel-based liposomes lipid nanoparticles particular development. Nanodelivery is anticipated to impact coming years improve patients.

Language: Английский

Citations

2