The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types. Molecular pathology has therefore become fundamental not only to inform on tumor diagnosis and prognosis but also to drive therapeutic decisions in daily practice. The introduction of next-generation sequencing technologies and the rising number of large-scale tumor molecular profiling programs across institutions worldwide have revolutionized the field of precision oncology. As comprehensive genomic analyses become increasingly available in both clinical and research settings, healthcare professionals are faced with the complex tasks of result interpretation and translation. This review summarizes the current and upcoming approaches to implement precision cancer medicine, highlighting the challenges and potential solutions to facilitate the interpretation and to maximize the clinical utility of molecular profiling results. We describe novel molecular characterization strategies beyond tumor DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analyses. We also review current and potential applications of liquid biopsies to evaluate blood-based biomarkers, such as circulating tumor cells and circulating nucleic acids. Last, lessons learned from the existing limitations of genotype-derived therapies provide insights into ways to expand precision medicine beyond genomics.

中文翻译：

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精准癌症治疗的分子分析。

在过去十年中，可药物治疗的肿瘤特异性分子畸变的数量大幅增加，几种癌症类型的生物标志物匹配疗法获得了显着的生存获益。因此，分子病理学不仅成为肿瘤诊断和预后的基础，而且还成为日常实践中推动治疗决策的基础。新一代测序技术的引入以及全球各机构大规模肿瘤分子分析项目数量的不断增加，彻底改变了精准肿瘤学领域。随着全面的基因组分析在临床和研究环境中的应用越来越广泛，医疗保健专业人员面临着结果解释和翻译的复杂任务。本综述总结了当前和即将实施的精准癌症医学的方法，强调了促进分子分析结果的解释和最大化临床效用的挑战和潜在的解决方案。我们描述了肿瘤 DNA 测序之外的新颖分子表征策略，例如转录组学、免疫表型分析、表观遗传分析和单细胞分析。我们还回顾了液体活检在评估血液生物标志物（例如循环肿瘤细胞和循环核酸）方面的当前和潜在应用。最后，从基因型衍生疗法的现有局限性中吸取的经验教训为将精准医学扩展到基因组学之外的方法提供了见解。