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胰腺癌的靶向治疗:精准医学的新时代。

Targeted Therapies in Pancreatic Cancer: A New Era of Precision Medicine.

作者信息

Li Bingyu, Zhang Qiong, Castaneda Claire, Cook Shelly

机构信息

University of Wisconsin Hospitals and Clinics, Madison, WI 53792-2460, USA.

School of Medicine, Tongji University, Shanghai 200092, China.

出版信息

Biomedicines. 2024 Sep 25;12(10):2175. doi: 10.3390/biomedicines12102175.

Abstract

Pancreatic ductal adenocarcinoma (PDAC), a leading cause of cancer mortality in the United States, presents significant treatment challenges due to its late diagnosis and poor prognosis. Despite advances, the five-year survival rates remain dismally low, with only a fraction of patients eligible for potentially curative surgical interventions. This review aims to comprehensively examine the current landscape of targeted therapies in PDAC, focusing on recent developments in precision medicine approaches. We explore various molecular targets, including mutations, DNA damage repair deficiencies, mismatch repair pathway alterations, and rare genetic fusions. The review discusses emerging therapies, such as PARP inhibitors, immune checkpoint inhibitors, and novel targeted agents, like RET and NTRK inhibitors. We analyze the results of key clinical trials and highlight the potential of these targeted approaches in specific patient subgroups. Recent developments in PDAC research have emphasized precision oncology, facilitated by next-generation sequencing and the identification of genetic and epigenetic alterations. This approach tailors treatments to individual genetic profiles, improving outcomes and reducing side effects. Significant strides have been made in classifying PDAC into various subtypes, enhancing therapeutic precision. The identification of specific mutations in genes like , along with advancements in targeted therapies, including small molecule inhibitors, offers new hope. Furthermore, emerging therapies targeting DNA repair pathways and immunotherapeutic strategies also show promising results. As research evolves, integrating these targeted therapies with conventional treatments might improve survival rates and quality of life for PDAC patients, underscoring the shift towards a more personalized treatment paradigm.

摘要

胰腺导管腺癌(PDAC)是美国癌症死亡的主要原因之一,由于其诊断较晚且预后较差,带来了重大的治疗挑战。尽管取得了进展,但其五年生存率仍然极低,只有一小部分患者有资格接受可能治愈性的手术干预。本综述旨在全面审视PDAC靶向治疗的现状,重点关注精准医学方法的最新进展。我们探讨了各种分子靶点,包括突变、DNA损伤修复缺陷、错配修复途径改变以及罕见的基因融合。该综述讨论了新兴疗法,如PARP抑制剂、免疫检查点抑制剂,以及新型靶向药物,如RET和NTRK抑制剂。我们分析了关键临床试验的结果,并强调了这些靶向方法在特定患者亚组中的潜力。PDAC研究的最新进展强调了精准肿瘤学,这得益于下一代测序以及基因和表观遗传改变的识别。这种方法根据个体基因谱定制治疗方案,改善治疗效果并减少副作用。在将PDAC分类为各种亚型方面已经取得了重大进展,提高了治疗的精准性。在诸如等基因中特定突变的识别,以及包括小分子抑制剂在内的靶向治疗的进展,带来了新的希望。此外,针对DNA修复途径的新兴疗法和免疫治疗策略也显示出有前景的结果。随着研究的不断发展,将这些靶向疗法与传统治疗相结合可能会提高PDAC患者的生存率和生活质量,突显了向更加个性化治疗模式的转变。

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