宫颈癌类器官与药物筛选

Abstract Cervical cancer, driven mainly by human papillomavirus (HPV) infection, remains one of the most common malignant tumors among women worldwide, posing significant challenges in treatment and drug development. Traditional two‐dimensional (2D) cell culture models fail to accurately replicate the in vivo tumor microenvironment (TME), especially HPV‐driven oncogenic signaling, immune contexture, and stromal interactions unique to cervical cancer, limiting their predictive value for therapeutic efficacy (Y. Liu, H. Ai. Comprehensive insights into human papillomavirus and cervical cancer: pathophysiology, screening, and vaccination strategies. Biochim Biophys Acta Rev Cancer. 2024;1879(6):189192). Hydrogels have emerged as promising biomaterials for constructing three‐dimensional (3D) tumor models due to their tunable physicochemical properties, excellent biocompatibility, and ability to mimic the extracellular matrix. This review focuses on hydrogel applications in 3D cervical cancer TME modeling, with an emphasis on recapitulating HPV‐driven biology, immune‐stromal crosstalk, and stromal interactions, emphasizing their role in simulating key aspects of tumor biology such as cell–cell and cell–matrix interactions, hypoxia, and drug resistance. Recent advances in hydrogel‐based 3D models for high‐throughput drug screening are critically analyzed, highlighting their potential to improve the precision of cervical cancer treatment and accelerate novel drug discovery. However, critical challenges including high cost, limited industrial scalability, technical complexity, and strict regulatory constraints remain to be addressed to realize their full translational potential. By integrating current research findings, this review aims to provide a theoretical framework and technical guidance for future studies focused on enhancing the physiological relevance of in vitro cervical cancer models and optimizing therapeutic strategies.

… , enables simultaneous evaluation of drug efficacy against metastasis and angiogenesis, a … potential for drug screening but also offers insights into mechanistic studies, drug discovery, …

Background Despite advancements in treatment protocols, breast and cervical cancer are the leading causes of cancer-associated deaths in Indian women. Therefore, there is a need to develop more effective treatment strategies and better tumor models to test novel therapeutics. This study reports the development of a bioengineered three-dimensional (3D) model that can mimic in vivo tumors and be used to understand disease pathophysiology, as well as for drug testing/screening applications. Methodology The liquid overlay method was used to generate 3D spheroids of uniform size, based on breast (MDA-MB-231) and cervical (HeLa and CaSki) cancer cell lines. After this, they were embedded in collagen type I. The collagen-embedded spheroids were then subjected to live/dead staining, viability study, and expression of epithelial-mesenchymal transition (EMT) markers at predetermined time points. The 3D spheroids were also subjected to anti-cancer drug testing, followed by a viability assay. The software used for analysis was GraphPad Prism 8.4 (Dotmatics, Boston, Massachusetts, United States) and MS Excel (Microsoft Corporation, Redmond, Washington, United States). Results Uniform-sized, single spheroids for three different cell lines, MDA-MB-231, HeLa, and CaSki, were successfully generated using the liquid overlay technique. There was a significant increase in the viability of 3D spheroids after day 3 of incubation when compared with day 1. Live/dead staining showed the presence of dead cells in the core of the 3D spheroids. Further, EMT markers such as twist, N-cadherin, and fibronectin were found to be elevated in the case of 3D spheroids as compared to the two-dimensional (2D) culture of cancer cells. Additionally, the IC50 values of MDA-MB-231, HeLa, and CaSki spheroids following treatment with an anti-cancer drug, cisplatin, were found to be approximately four to five-fold higher than in the 2D culture. Conclusion The collagen-embedded 3D spheroid model is a robust model that can be used for the generation of 3D spheroids based on various cancer cell lines, recapitulating the properties of solid tumors in vivo. The model further demonstrates its potential to be used as a drug screening platform and can be used for the generation of patient tumor-derived 3D spheroids in the future.

Simple Summary Appropriate testing models are imperative to facilitate the discovery of effective personalized treatments against different cancers, including advanced cervical cancer. This review provides a comprehensive overview of the currently available three-dimensional (3D) models of cervical cancer and their significance in pre-clinical and clinical studies. The review emphasizes the potential of 3D tumor models, such as spheroids from cervical cancer cell lines and patient-derived organoids, to evaluate novel therapies, particularly immunotherapies that target tumor cells and modulate the tumor microenvironment. Notably, the cervical cancer field is underdeveloped regarding use of 3D tumor models, and there is an increasing need to develop appropriate models to address this clinical burden, which will aid in personalized treatment discovery. Abstract Cervical cancer is one of the most common malignant diseases in women worldwide. Despite the global introduction of a preventive vaccine against the leading cause of cervical cancer, human papillomavirus (HPV) infection, the incidence of this malignant disease is still very high, especially in economically challenged areas. New advances in cancer therapy, especially the rapid development and application of different immunotherapy strategies, have shown promising pre-clinical and clinical results. However, mortality from advanced stages of cervical cancer remains a significant concern. Precise and thorough evaluation of potential novel anti-cancer therapies in pre-clinical phases is indispensable for efficient development of new, more successful treatment options for cancer patients. Recently, 3D tumor models have become the gold standard in pre-clinical cancer research due to their capacity to better mimic the architecture and microenvironment of tumor tissue as compared to standard two-dimensional (2D) cell cultures. This review will focus on the application of spheroids and patient-derived organoids (PDOs) as tumor models to develop novel therapies against cervical cancer, with an emphasis on the immunotherapies that specifically target cancer cells and modulate the tumor microenvironment (TME).

… drug discovery. Almost in 100% of cases, high-risk HPV DNA has been found to be associated with cervical cancer. … FDA-approved drugs library was screened employing the developed …