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Review of precision cancer medicine: Evolution of the treatment paradigm.
Cancer Treatment Reviews ( IF 11.8 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.ctrv.2020.102019
Apostolia M Tsimberidou 1 , Elena Fountzilas 2 , Mina Nikanjam 3 , Razelle Kurzrock 3
Affiliation  

In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology.

中文翻译:

精准癌症医学回顾:治疗范式的演变。

近年来,生物技术的突破已导致与致癌相关的复杂且独特的生物学特征的鉴定。肿瘤和游离 DNA 分析、免疫标记以及蛋白质组和 RNA 分析用于识别这些特征,以优化个体患者的抗癌治疗。因此,临床试验不断发展,从以肿瘤类型为中心转向以基因为导向、与组织学无关,并针对生物标志物分析进行创新的适应性设计,以改善治疗结果。已经进行了大量的精准医学试验。这些试验中的大多数表明,在肿瘤类型和特定癌症中,与非匹配治疗相比,匹配治疗具有更好的结果。为了改善精准医疗的实施,这种方法应该在病程早期使用,患者应该有完整的肿瘤分析并获得有效的匹配治疗。为了克服肿瘤生物学的复杂性,将基因靶向治疗与免疫靶向方法(例如,检查点封锁、个性化疫苗和/或嵌合抗原受体T细胞)、激素疗法、化疗和/或新型药物相结合的临床试验应该被考虑。这些研究应针对肿瘤生物学异常的动态变化,消除微小残留疾病,并根除对治疗产生耐药性的显着亚克隆。通过使用先进的计算机数据处理能力促进现实世界数据的挖掘和扩展,可能有助于验证信息以预测药物的新应用。在这篇综述中,我们总结了临床试验,并讨论了加速实施精准肿瘤学的挑战和机遇。
更新日期:2020-03-31
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