迫切需要改善原发灶不明的癌症 (CUP) 患者的诊断和治疗选择。在这篇综述中，我们讨论了 CUP 中分子分析的发展前景。分子分析正在被 CUP 患者的诊断检查所接受，肿瘤突变分析现在已在国际 CUP 指南中描述。尽管利用基因表达和 DNA 甲基化的组织源 (ToO) 分子测试已经存在了一段时间，但其临床益处仍不清楚。利用全基因组测序和机器学习算法的新技术在确定 ToO 方面显示出希望，但在临床应用之前还需要进一步研究。最近的一项国际临床试验发现，与单独化疗相比，接受基于全面 DNA 测序的分子引导治疗的患者改善了无进展生存期，证实了在患者旅程早期进行基因组分析的效用。小型 2 期试验表明，一些 CUP 患者对免疫治疗有反应，但选择患者进行治疗的最佳方法尚不清楚。CUP 的治疗需要采用多方面的方法，结合临床、组织病理学、放射学和分子测序结果，以协助识别可能的 ToO 和临床上可行的基因组改变。快速识别可能受益于位点特异性治疗、靶向治疗和/或免疫治疗的 CUP 患者子集将改善患者的治疗结果。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。

There is significant need to improve diagnostic and therapeutic options for patients with cancer of unknown primary (CUP). In this review, we discuss the evolving landscape of molecular profiling in CUP.Molecular profiling is becoming accepted into the diagnostic work-up of CUP patients with tumour mutation profiling now described in international CUP guidelines. Although tissue-of-origin (ToO) molecular tests utilising gene-expression and DNA methylation have existed some time, their clinical benefit remains unclear. Novel technologies utilising whole genome sequencing and machine learning algorithms are showing promise in determining ToO, however further research is required prior to clinical application. A recent international clinical trial found patients treated with molecularly-guided therapy based on comprehensive-panel DNA sequencing had improved progression-free survival compared to chemotherapy alone, confirming utility of performing genomic profiling early in the patient journey. Small phase 2 trials have demonstrated that some CUP patients are responsive to immunotherapy, but the best way to select patients for treatment is not clear.Management of CUP requires a multifaceted approach incorporating clinical, histopathological, radiological and molecular sequencing results to assist with identifying the likely ToO and clinically actionable genomic alternations. Rapidly identifying a subset of CUP patients who are likely to benefit from site specific therapy, targeted therapy and/or immunotherapy will improve patient outcomes.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.