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用于治疗脊柱骨肉瘤的新策略。

Novel therapeutic strategies for spinal osteosarcomas.

机构信息

Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon.

Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.

出版信息

Semin Cancer Biol. 2020 Aug;64:83-92. doi: 10.1016/j.semcancer.2019.05.018. Epub 2019 May 29.

DOI:10.1016/j.semcancer.2019.05.018
PMID:31152785
Abstract

At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.

摘要

在第三个千年的曙光初现之际,癌症已成为 21 世纪人类的祸根,仍然是一个主要的全球公共卫生负担,影响着福利和预期寿命。脊柱骨肉瘤是一种原发性脊柱恶性肿瘤,是一种罕见且具有挑战性的肿瘤疾病。在化疗、放疗和手术等传统治疗方法都已用尽的情况下,目前尚无其他替代疗法可用于治疗脊柱骨肉瘤。肿瘤存活的决定性特征是癌细胞通过各种手段抵御免疫原性损耗和细胞凋亡的能力。其中一些生物标志物,即免疫检查点,最近已被用作骨肉瘤和许多其他不同癌症的可靶向药物。这些使用重振的免疫治疗方法所取得的有希望的进展,可能会导致脊柱骨肉瘤疾病负担的显著减少,并相应地提高生存率。在这篇综述中,我们提供了脊柱骨肉瘤的背景信息,并详细阐述了肿瘤微环境中复杂生态系统导致癌症免疫逃逸的作用,这是目前受到广泛关注的问题。在肿瘤微环境这一部分之后,我们简要回顾了癌症免疫的历史。此外,我们还借鉴了其他骨骼部位(靠近骺板的四肢长骨)发生骨肉瘤的治疗经验,探讨了应用基于免疫的工具(如免疫检查点抑制剂和疫苗)的可能性,并提请注意免疫检查点阻滞剂的不良反应。最后,我们描述了 CRISPR/Cas9 这一新型生物技术,它将有助于实现个体化药物治疗方法。

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