Recent advancements in oncology have led to the development of histology-agnostic therapies, which target genetic alterations irrespective of the tumor’s tissue of origin. This review aimed to provide a comprehensive update on the current state of histology-agnostic drug development, focusing on key therapies, including pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib plus trametinib, selpercatinib, trastuzumab deruxtecan, and reprotrectinib. We performed a detailed analysis of each therapy’s mechanism of action, clinical trial outcomes, and associated biomarkers. The review further explores challenges in drug resistance, such as adaptive signaling pathways and neoantigen variability, as well as diagnostic limitations in identifying optimal patient populations. While these therapies have demonstrated efficacy in various malignancies, significant hurdles remain, including intratumoral heterogeneity and resistance mechanisms that diminish treatment effectiveness. We propose considerations for refining trial designs and emerging biomarkers, such as tumor neoantigen burden, to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers.
肿瘤学领域的最新进展催生了组织学无关疗法的发展，这类疗法针对基因改变进行治疗，而不考虑肿瘤的组织来源。本综述旨在全面更新当前组织学无关药物研发现状，重点探讨包括帕博利珠单抗、拉罗替尼、恩曲替尼、多塔利单抗、达拉非尼联合曲美替尼、塞尔帕替尼、德曲妥珠单抗及瑞普替尼在内的关键疗法。我们对每种疗法的作用机制、临床试验结果及相关生物标志物进行了详细分析。综述进一步探讨了耐药性挑战，如适应性信号通路和新抗原变异性，以及识别最佳患者群体时存在的诊断局限性。尽管这些疗法已在多种恶性肿瘤中显示出疗效，但仍面临重大障碍，包括肿瘤内异质性和降低治疗效果的耐药机制。我们提出了优化试验设计的考量因素，并探讨了肿瘤新抗原负荷等新兴生物标志物以改进患者筛选。这些发现揭示了组织学无关疗法在精准肿瘤学中的变革潜力，同时强调需要持续开展研究以优化其应用并克服现有障碍。
肿瘤(癌症)患者之家