Yee Nelson S, Kazi Abid A, Yee Rosemary K
Penn State Hershey Cancer Institute, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA.
Curr Clin Pharmacol. 2015;10(4):256-66. doi: 10.2174/1574884710666151020100640.
The purpose of this article is to provide a critical review of the current systemic treatment and the emerging targeted therapeutic strategies in pancreatic adenocarcinoma. Cytotoxic chemotherapeutic drugs have been used for palliative treatment of pancreatic adenocarcinoma, as well as for neoadjuvant therapy to facilitate surgical resection, and as adjuvant therapy to prevent tumor recurrence. The recent findings of early metastasis of cancer cells in pancreatic adenocarcinoma provide support for systemic therapy even in the case of small and localized tumors. However, the clinical benefits of systemic chemotherapy are generally limited and it is typically associated with a multitude of toxicities. Cancer-specific therapies with improved efficacy and safety are urgently needed. Tremendous advances have been made in understanding the biology and genetic regulation of normal and neoplastic development of the pancreas. These have led to identification of molecular targets in pancreatic cancer cells, the tumor microenvironment, and the cancer stem cells. Tumor-specific modalities are emergent by exploitation of the aberrant signaling pathways and molecular alterations in pancreatic cancer with the goals of improving treatment response. Integrative approaches that combine various targeting strategies with molecular bioinformatics will hopefully lead to the development of personalized therapies that may produce a positive impact on the quality of life and survival for patients with this deadly disease.
本文旨在对目前胰腺癌的全身治疗及新兴的靶向治疗策略进行批判性综述。细胞毒性化疗药物已用于胰腺癌的姑息治疗，以及用于促进手术切除的新辅助治疗，还用于预防肿瘤复发的辅助治疗。胰腺癌中癌细胞早期转移的最新发现为即使是小的局限性肿瘤也进行全身治疗提供了支持。然而，全身化疗的临床益处通常有限，且通常伴有多种毒性。迫切需要疗效和安全性更高的癌症特异性疗法。在理解胰腺正常和肿瘤发生发展的生物学及遗传调控方面已取得了巨大进展。这些进展已导致在胰腺癌细胞、肿瘤微环境和癌症干细胞中鉴定出分子靶点。通过利用胰腺癌中异常的信号通路和分子改变来开发肿瘤特异性治疗方法，目标是改善治疗反应。将各种靶向策略与分子生物信息学相结合的综合方法有望导致个性化疗法的发展，这可能会对这种致命疾病患者的生活质量和生存率产生积极影响。
