Introduction
癌症护理已朝着基于基因组化妆的个体量身定制的新的个性化浪潮迈进，结束了传统医学的“千篇一律”方法。组织/肿瘤/部位不足的疗法是个性化医学的重要细分。这些疗法靶向特定的基因组生物标志物，无论其位置和组织学如何，都在不同类型的癌症上共享，这与靶向限于特定器官或组织的特定生物标志物阳性肿瘤的疗法不同。通过消除肿瘤类型的组织限制，这种新时代的概念彻底改变了精密医学。
进度
传统上，肿瘤学家根据肿瘤起源的器官或组织对患者进行了治疗。随着分子诊断的进步，预计分子靶向治疗将对一系列生物标志物定义的肿瘤类型有效，而不是仅限于肿瘤起源部位。但是，肿瘤部位的分子和细胞异质性在可能受益于其的患者人群方面构成了独特的情况。开发的靶向疗法可以针对EGFR，ALK，ROS1，HER2，KIT，BRAF和GELLINE BRCA1/2的特定基因组改变，但仅针对特定的肿瘤类型（例如，具有EML4-Alk Fusion和HER2的肺癌中的ALK抑制剂/HER2/NEU阳性乳腺癌中的NEU阻塞）。配备了免疫疗法的出现和肿瘤新抗原的发现，再加上高通量基因组测序的进展，组织 - 敏锐的癌症药物发育得以实现。
2012年，约翰·霍普金斯大学（Johns Hopkins University）的科学家理论上，具有不匹配修复基因改变的肿瘤产生了大量的新抗原，可以引起免疫反应，应特别敏感，对免疫检查点抑制剂特别敏感，这些抑制剂识别这些反应并刺激T细胞反应。他们的成功研究为组织 - 敏锐的癌症疗法的出现铺平了道路。
The biomarker targets of tissue-agnostic therapies
图1中描述了一些对组织类型不可知的癌症基因的畸变。
挑战
Tumor-agnostic therapies challenge the existing diagnostic, regulatory and HTA frameworks, and market entry pathways. Patient screening may also be a hurdle as universal testing for rare biomarkers may not be covered through insurance due to high costs. These drugs also come with an expensive price tag. Testing of these therapies in a basket trial may be a long process due to recruitment hurdles owing to small sample sizes. Furthermore, a histology-independent development model is not going to universally work for all tumor-agnostic therapies – the same level of antitumor activity might not occur across different malignancies. Therefore, tumor-agnostic therapies cannot entirely replace conventional histology-based treatments.
The road to future
As we embrace a biomarker-based approach, the breadth and depth of precision medicine is gaining the much-deserved spotlight and is being recurrently highlighted in reputable cancer conferences in recent years – the American Society of Clinical Oncology (ASCO) annual meeting 2018 explored the theme of ‘Delivering Discoveries: Expanding the Reach of Precision Medicine’ and the American Association for Cancer Research (AACR) annual meeting 2019 explored the theme of ‘Individualized Patient Care’. Basket trials, such as NCI-MATCH and NCI-COG Pediatric MATCH, that recruit patients of several tumor types with rare mutations to study responses across different biomarkers, are being conducted to investigate potential therapies and to provide data to expand the potential population of patients who can respond to a biomarker target. Patient recruitment in basket trials can be informed by employing cutting-edge comprehensive diagnostic panels that use next generation sequencing for genomic profiling. Collaboration among regulatory and HTA bodies, clinical investigators, physicians, pharma companies and patient groups is critical in bringing more tissue-agnostic therapies to bedside.
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