Cell Biology Unit, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Indivumed GmbH, Hamburg, Germany.
FEBS J. 2021 Nov;288(21):6142-6158. doi: 10.1111/febs.15788. Epub 2021 Mar 19.
The past decades have seen tremendous developments with respect to "specific" therapeutics that target key signaling molecules to conquer cancer. The key advancements with multiomics technologies, especially genomics, have allowed physicians and molecular oncologists to design "tailor-made" solutions to the specific oncogenes that are deregulated in individual patients, a strategy which has turned out to be successful though the patients quickly develop resistance. The swift integration of multidisciplinary approaches has led to the development of "next generation" therapeutics and, with synergistic therapeutic regimes combined with immune checkpoint inhibitors to reactivate the dampened immune response, has provided the much-needed promise for cancer patients. Despite these advances, a large portion of the druggable genome remains understudied, and the role of druggable genome in the immune system needs further attention. Establishment of patient-derived organoid models has fastened the preclinical validation of novel therapeutics for swift clinical translation. We summarized the current advances and challenges and also stress the importance of biobanking and collection of longitudinal data sets with structured clinical information, as well as the critical role these "high content data sets" will play in designing new therapeutic regimes in a tailor-made fashion.
在过去几十年中，针对关键信号分子的“特异性”疗法取得了巨大进展，从而攻克癌症。多组学技术（尤其是基因组学）的主要进展，使医生和分子肿瘤学家能够针对个别患者中失调的特定致癌基因设计“定制”解决方案，尽管患者很快产生耐药性，但这种策略已被证明是成功的。多学科方法的迅速融合导致了“下一代”疗法的发展，并且通过联合治疗方案和免疫检查点抑制剂来重新激活被抑制的免疫反应，为癌症患者带来了急需的希望。尽管取得了这些进展，但大部分可用药基因组仍未得到充分研究，可用药基因组在免疫系统中的作用仍需要进一步关注。建立患者来源的类器官模型加速了新型疗法的临床前验证，以便快速进行临床转化。我们总结了当前的进展和挑战，并强调了生物库的建立和具有结构化临床信息的纵向数据集的收集的重要性，以及这些“高内涵数据集”在设计定制治疗方案方面将发挥的关键作用。
