Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
Curr Pharm Des. 2011;17(21):2221-38. doi: 10.2174/138161211796957427.
Human pancreatic cancer remains a highly malignant disease with almost similar incidence and mortality despite extensive research. Many targeted therapies are under development. However, clinical investigation showed that single targeted therapies and most combined therapies were not able to improve the prognosis of this disease, even though some of these therapies had excellent anti-tumor effects in pre-clinical models. Cross-talk between cell proliferation signaling pathways may be an important phenomenon in pancreatic cancer, which may result in cancer cell survival even though some pathways are blocked by targeted therapy. Pancreatic cancer may possess different characteristics and targets in different stages of pathogenesis, maintenance and metastasis. Sensitivity to therapy may also vary for cancer cells at different stages. The unique pancreatic cancer structure with abundant stroma creates a tumor microenvironment with hypoxia and low blood perfusion rate, which prevents drug delivery to cancer cells. In this review, the most commonly investigated targeted therapies in pancreatic cancer treatment are discussed. However, how to combine these targeted therapies and/or combine them with chemotherapy to improve the survival rate of pancreatic cancer is still a challenge. Genomic and proteomic studies using pancreatic cancer samples obtained from either biopsy or surgery are recommended to individualize tumor characters and to perform drug sensitivity study in order to design a tailored therapy with minimal side effects. These studies may help to further investigate tumor pathogenesis, maintenance and metastasis to create cellular expression profiles at different stages. Integration of the information obtained needs to be performed from multiple levels and dimensions in order to develop a successful targeted therapy.
尽管进行了广泛的研究，但人类胰腺癌仍然是一种高度恶性的疾病，其发病率和死亡率几乎相似。许多靶向治疗方法正在开发中。然而，临床研究表明，单一的靶向治疗和大多数联合治疗方法都不能改善这种疾病的预后，尽管这些治疗方法中的一些在临床前模型中具有出色的抗肿瘤作用。细胞增殖信号通路之间的串扰可能是胰腺癌的一个重要现象，即使某些通路被靶向治疗阻断，也可能导致癌细胞存活。胰腺癌在发病机制、维持和转移的不同阶段可能具有不同的特征和靶点。不同阶段的癌细胞对治疗的敏感性也可能不同。丰富基质的独特胰腺癌结构会产生缺氧和低血流灌注率的肿瘤微环境，从而阻止药物输送到癌细胞。在这篇综述中，讨论了胰腺癌治疗中最常研究的靶向治疗方法。然而，如何将这些靶向治疗方法结合起来，或者将它们与化疗结合起来，以提高胰腺癌的生存率，仍然是一个挑战。建议使用从活检或手术获得的胰腺癌样本进行基因组和蛋白质组研究，以确定肿瘤特征，并进行药物敏感性研究，从而设计副作用最小的个体化治疗方法。这些研究可能有助于进一步研究肿瘤的发病机制、维持和转移，以在不同阶段创建细胞表达谱。需要从多个层面和维度整合所获得的信息，以开发成功的靶向治疗方法。
