Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Expert Rev Anticancer Ther. 2024 Jul;24(7):525-565. doi: 10.1080/14737140.2024.2357802. Epub 2024 May 23.
Despite the considerable progress made in cancer treatment through the development of target therapies, pancreatic ductal adenocarcinoma (PDAC) continues to exhibit resistance to this category of drugs. As a result, chemotherapy combination regimens remain the primary treatment approach for this aggressive cancer.
In this review, we provide an in-depth analysis of past and ongoing trials on both well-known and novel targets that are being explored in PDAC, including PARP, EGFR, HER2, KRAS, and its downstream and upstream pathways (such as RAF/MEK/ERK and PI3K/AKT/mTOR), JAK/STAT pathway, angiogenesis, metabolisms, epigenetic targets, claudin, and novel targets (such as P53 and plectin). We also provide a comprehensive overview of the significant trials for each target, allowing a thorough glimpse into the past and future of target therapy.
The path toward implementing a target therapy capable of improving the overall survival of PDAC is still long, and it is unlikely that a monotherapy target drug will fulfill a meaningful role in addressing the complexity of this cancer. Thus, we discuss the future direction of target therapies in PDAC, trying to identify the more promising target and combination treatments, with a special focus on the more eagerly awaited ongoing trials.
尽管通过开发靶向治疗在癌症治疗方面取得了相当大的进展，但胰腺导管腺癌 (PDAC) 仍然对这一类药物具有耐药性。因此，化疗联合方案仍然是治疗这种侵袭性癌症的主要方法。
在这篇综述中，我们深入分析了过去和正在进行的针对 PDAC 中正在探索的知名和新型靶点的试验，包括 PARP、EGFR、HER2、KRAS 及其下游和上游途径（如 RAF/MEK/ERK 和 PI3K/AKT/mTOR）、JAK/STAT 途径、血管生成、代谢、表观遗传靶点、claudin 和新型靶点（如 P53 和 plectin）。我们还全面概述了每个靶点的重要试验，使人们能够全面了解靶向治疗的过去和未来。
在实施能够提高 PDAC 总生存率的靶向治疗方面，还有很长的路要走，而且单一疗法的靶向药物不太可能在解决这种癌症的复杂性方面发挥重要作用。因此，我们讨论了 PDAC 中靶向治疗的未来方向，试图确定更有前途的靶点和联合治疗方法，特别关注更受期待的正在进行的试验。
