Department of Proteomics, National Cancer Center Research Institute, Tokyo, Japan.
Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Sci. 2024 May;115(5):1378-1387. doi: 10.1111/cas.16123. Epub 2024 Feb 26.
The last few decades have seen remarkable strides in the field of cancer therapy. Precision oncology coupled with comprehensive genomic profiling has become routine clinical practice for solid tumors, the advent of immune checkpoint inhibitors has transformed the landscape of oncology treatment, and the number of cancer drug approvals has continued to increase. Nevertheless, the application of genomics-driven precision oncology has thus far benefited only 10%-20% of cancer patients, leaving the majority without matched treatment options. This limitation underscores the need to explore alternative avenues with regard to selecting patients for targeted therapies. In contrast with genomics-based approaches, proteomics-based strategies offer a more precise understanding of the intricate biological processes driving cancer pathogenesis. This perspective underscores the importance of integrating complementary proteomic analyses into the next phase of precision oncology to establish robust biomarker-drug associations and surmount challenges related to drug resistance. One promising technology in this regard is the reverse-phase protein array (RPPA), which excels in quantitatively detecting protein modifications, even with limited amounts of sample. Its cost-effectiveness and rapid turnaround time further bolster its appeal for application in clinical settings. Here, we review the current status of genomics-driven precision oncology, as well as its limitations, with an emphasis on drug resistance. Subsequently, we explore the application of RPPA technology as a catalyst for advancing precision oncology. Through illustrative examples drawn from clinical trials, we demonstrate its utility for unraveling the molecular mechanisms underlying drug responses and resistance.
过去几十年，癌症治疗领域取得了显著进展。精准肿瘤学结合全面的基因组分析已成为实体瘤常规临床实践，免疫检查点抑制剂的出现改变了肿瘤治疗领域的格局，癌症药物的批准数量也在不断增加。然而，迄今为止，基因组驱动的精准肿瘤学的应用仅使 10%-20%的癌症患者受益，大多数患者仍缺乏匹配的治疗选择。这一局限性突显了需要探索针对靶向治疗选择患者的替代途径。与基于基因组学的方法相比，基于蛋白质组学的策略提供了对推动癌症发病机制的复杂生物学过程更精确的理解。这一观点强调了将互补的蛋白质组学分析纳入精准肿瘤学的下一阶段以建立稳健的生物标志物-药物关联并克服与耐药性相关的挑战的重要性。在这方面，一种很有前途的技术是反相蛋白质阵列（RPPA），它在定量检测蛋白质修饰方面表现出色，即使样本量有限也是如此。其成本效益和快速周转时间进一步增强了其在临床环境中的应用吸引力。在这里，我们回顾了基于基因组学的精准肿瘤学的现状及其局限性，重点是耐药性。随后，我们探讨了 RPPA 技术的应用，作为推进精准肿瘤学的催化剂。通过从临床试验中得出的示例，我们展示了它在揭示药物反应和耐药性的分子机制方面的实用性。
