Sarah Cannon Research Institute, Nashville, TN.
Am Soc Clin Oncol Educ Book. 2020 May;40:309-318. doi: 10.1200/EDBK_100024.
As researchers learn more about tumor biology and the molecular mechanisms involved in tumorigenesis, metastasis, and tumor evolution, clinical trials are growing more complex and patient selection for clinical trials is becoming more specific. Rather than exploit certain phenotypic characteristics of tumor cells (e.g., rapid cell division and uncontrolled cell growth), pharmaceuticals targeting the genotypic causes of tumorigenesis are emerging. The sequencing of the human genome, advances in chemical techniques, and increased efficiency in drug target identification have changed the way drugs are developed. Now, more precise drugs targeting specific mutations within individual genes are being used to treat narrow patient populations harboring these specific driver mutations, often with greater efficacy and lower toxicity than traditional chemotherapeutic agents. This precision in drug development relies not only on the ability to design exquisitely specific pharmaceuticals but also to identify (with the same level of precision) the patients who are most likely to respond to those therapies. Robust screening techniques and adequate molecular oncology education are required to match the appropriate patient to precision therapies, and these same screening techniques provide the data necessary to advance to the next generation of drug development.
随着研究人员对肿瘤生物学和肿瘤发生、转移和肿瘤进化所涉及的分子机制有了更多的了解，临床试验变得越来越复杂，临床试验的患者选择也变得越来越具体。现在，针对个体基因中特定突变的更精确药物被用于治疗携带这些特定驱动突变的窄患者群体，其疗效通常比传统化疗药物更高，毒性更低。这种药物开发的精确性不仅依赖于设计高度特异性药物的能力，还依赖于识别（同样精确）最有可能对这些治疗产生反应的患者。需要强大的筛选技术和充分的分子肿瘤学教育来将合适的患者与精准疗法相匹配，而这些相同的筛选技术也提供了推进下一代药物开发所需的数据。
