Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers
Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers
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DOI：
10.1007/s10439-020-02704-9
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发表时间：
2021-01-05
影响因子：
3.8
通讯作者：
Nikkhah, Mehdi
中科院分区：
文献类型：
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作者：
Amirghasemi, Farbod;Adjei-Sowah, Emmanuela;Nikkhah, Mehdi
癌症的负担在社会中持续增加，并对许多患者的生活产生负面影响。由于目前治疗策略的高成本，开发廉价的临床前平台以加速抗癌药物发现的过程以改善癌症患者，特别是女性患者的结果是一个关键的未满足的需求。目前许多方法采用昂贵的动物模型，不仅存在伦理问题，而且往往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。虽然这种治疗技术是有效的，但由于各种复杂因素，如肿瘤内异质性和肿瘤微环境（TME）内的混杂因素，结果并不总是积极的。发生转移性疾病的患者仍然预后不良。为此，最近的努力试图使用3D微工程平台来提高抗癌药物筛选的预测能力和有效性，最终开发个性化疗法。微工程分析的快速特征，例如微流体，已经导致肿瘤芯片技术平台的发展的进步，其已经显示出有意义的和生理相关的抗癌药物发现和筛选的巨大潜力。三维微尺度模型提供了前所未有的能力来揭示癌症的生物学复杂性，并以及时和资源有效的方式揭示抗癌药物耐药性的机制。在这篇综述中，我们讨论了最近的进展，微工程肿瘤模型的发展，抗癌药物的发现和筛选，在女性相关的癌症。我们特别关注与女性有关的癌症，以提请注意正在采取的各种方法，以提高因性别差异而被诊断患有癌症的妇女的生存率。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，这使得目前女性的治疗策略复杂化。我们强调了3D微尺度平台（包括3D肿瘤球体、微流体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，如化疗耐药性、肿瘤内异质性、药物毒性、我们还介绍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，我们将提供我们对所讨论的平台技术的优势的看法。
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.