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Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers
Annals of Biomedical Engineering ( IF 3.8 ) Pub Date : 2021-01-05 , DOI: 10.1007/s10439-020-02704-9
Farbod Amirghasemi 1 , Emmanuela Adjei-Sowah 1 , Barbara A Pockaj 2 , Mehdi Nikkhah 1, 3
Affiliation  

The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies, there is a crucial unmet need to develop inexpensive preclinical platforms to accelerate the process of anti-cancer drug discovery to improve outcomes in cancer patients, most especially in female patients. Many current methods employ expensive animal models which not only present ethical concerns but also do not often accurately predict human physiology and the outcomes of anti-cancer drug responsiveness. Conventional treatment approaches for cancer generally include systemic therapy after a surgical procedure. Although this treatment technique is effective, the outcome is not always positive due to various complex factors such as intratumor heterogeneity and confounding factors within the tumor microenvironment (TME). Patients who develop metastatic disease still have poor prognosis. To that end, recent efforts have attempted to use 3D microengineered platforms to enhance the predictive power and efficacy of anti-cancer drug screening, ultimately to develop personalized therapies. Fascinating features of microengineered assays, such as microfluidics, have led to the advancement in the development of the tumor-on-chip technology platforms, which have shown tremendous potential for meaningful and physiologically relevant anti-cancer drug discovery and screening. Three dimensional microscale models provide unprecedented ability to unveil the biological complexities of cancer and shed light into the mechanism of anti-cancer drug resistance in a timely and resource efficient manner. In this review, we discuss recent advances in the development of microengineered tumor models for anti-cancer drug discovery and screening in female-related cancers. We specifically focus on female-related cancers to draw attention to the various approaches being taken to improve the survival rate of women diagnosed with cancers caused by sex disparities. We also briefly discuss other cancer types like colon adenocarcinomas and glioblastoma due to their high rate of occurrence in females, as well as the high likelihood of sex-biased mutations which complicate current treatment strategies for women. We highlight recent advances in the development of 3D microscale platforms including 3D tumor spheroids, microfluidic platforms as well as bioprinted models, and discuss how they have been utilized to address major challenges in the process of drug discovery, such as chemoresistance, intratumor heterogeneity, drug toxicity, etc. We also present the potential of these platform technologies for use in high-throughput drug screening approaches as a replacements of conventional assays. Within each section, we will provide our perspectives on advantages of the discussed platform technologies.



中文翻译:

用于女性相关癌症的抗癌药物发现的微工程 3D 肿瘤模型

癌症的负担在社会中不断增加,并对许多患者的生活产生负面影响。由于当前治疗策略的高成本,迫切需要开发廉价的临床前平台来加速抗癌药物发现过程,以改善癌症患者的预后,尤其是女性患者。许多当前的方法采用昂贵的动物模型,这些模型不仅存在伦理问题,而且通常不能准确预测人体生理学和抗癌药物反应性的结果。癌症的常规治疗方法通常包括外科手术后的全身治疗。虽然这种治疗方法很有效,由于肿瘤内异质性和肿瘤微环境(TME)内的混杂因素等各种复杂因素,结果并不总是积极的。发生转移性疾病的患者预后仍然很差。为此,最近的努力试图使用 3D 微工程平台来增强抗癌药物筛选的预测能力和功效,最终开发个性化疗法。微工程化验(如微流体)的迷人特征推动了片上肿瘤技术平台的发展,这些平台显示出在发现和筛选有意义的和生理相关的抗癌药物方面的巨大潜力。三维微尺度模型提供了前所未有的能力,可以揭示癌症的生物学复杂性,并及时和资源有效地揭示抗癌药物耐药机制。在这篇综述中,我们讨论了开发用于女性相关癌症的抗癌药物发现和筛查的微工程肿瘤模型的最新进展。我们特别关注与女性相关的癌症,以提请注意为提高被诊断患有由性别差异引起的癌症的女性的生存率而采取的各种方法。我们还简要讨论了其他癌症类型,如结肠腺癌和胶质母细胞瘤,因为它们在女性中的发生率很高,以及性别偏见突变的可能性很高,这使当前的女性治疗策略变得复杂。我们重点介绍了 3D 微型平台(包括 3D 肿瘤球体、微流控平台以及生物打印模型)开发的最新进展,并讨论了它们如何用于解决药物发现过程中的主要挑战,例如化学抗性、肿瘤内异质性、药物毒性等。我们还展示了这些平台技术在高通量药物筛选方法中作为传统检测方法的替代品的潜力。在每个部分中,我们将就所讨论的平台技术的优势提供我们的观点。肿瘤内异质性、药物毒性等。我们还展示了这些平台技术在高通量药物筛选方法中作为常规检测替代品的潜力。在每个部分中,我们将就所讨论的平台技术的优势提供我们的观点。肿瘤内异质性、药物毒性等。我们还展示了这些平台技术在高通量药物筛选方法中作为常规检测替代品的潜力。在每个部分中,我们将就所讨论的平台技术的优势提供我们的观点。

更新日期:2021-01-06
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