Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Medical Department III for Haematology and Oncology, School of Medicine, Technical University of Munich, Munich, Germany.
Virchows Arch. 2024 Feb;484(2):169-179. doi: 10.1007/s00428-023-03702-7. Epub 2023 Nov 20.
Medical oncology is rapidly evolving with the implementation of personalized, targeted therapies. Advances in molecular diagnostics and the biologic understanding of cancer pathophysiology led to the identification of specific genetic alterations as drivers of cancer progression. Further, improvements in drug development enable the direct interference with these pathways, which allow tailoring personalized treatments based on a distinct molecular characterization of tumors. Thereby, we are currently experiencing a paradigm-shift in the treatment of cancers towards cancer-type agnostic, molecularly targeted, personalized therapies. However, this concept has several important hurdles and limitations to overcome to ultimately increase the proportion of patients benefitting from the precision oncology approach. These include the assessment of clinical relevancy of identified alterations, capturing and interpreting levels of heterogeneity based on intra-tumoral or time-dependent molecular evolution, and challenges in the practical implementation of precision oncology in routine clinical care. In the present review, we summarize the current state of cancer-agnostic precision oncology, discuss the concept of molecular tumor boards, and consider current limitations of personalized cancer therapy. Further, we provide an outlook towards potential future developments including the implementation of functionality assessments of identified genetic alterations and the broader use of liquid biopsies in order to obtain more comprehensive and longitudinal genetic information that might guide personalized cancer therapy in the future.
医学肿瘤学随着个性化、靶向治疗的实施正在迅速发展。分子诊断学的进步和对癌症病理生理学的生物学理解,导致了特定基因改变作为癌症进展驱动因素的识别。此外,药物开发的改进使得能够直接干扰这些途径,从而能够根据肿瘤的独特分子特征定制个性化治疗。因此,我们目前正在经历一种治疗癌症的范式转变,即针对癌症类型、分子靶向、个性化治疗。然而,为了最终增加受益于精准肿瘤学方法的患者比例,这一概念有几个重要的障碍和局限性需要克服。这些障碍和局限性包括评估所确定的改变的临床相关性,基于肿瘤内或时间依赖性分子进化来捕获和解释异质性水平,以及在常规临床护理中实施精准肿瘤学的实际挑战。在本综述中,我们总结了癌症无偏倚精准肿瘤学的现状,讨论了分子肿瘤委员会的概念,并考虑了个性化癌症治疗的当前局限性。此外,我们对未来的潜在发展进行了展望,包括对所确定的遗传改变的功能评估的实施以及液体活检的更广泛应用,以获得更全面和纵向的遗传信息,从而指导未来的个性化癌症治疗。