Adamska Aleksandra, Domenichini Alice, Falasca Marco
Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
Int J Mol Sci. 2017 Jun 22;18(7):1338. doi: 10.3390/ijms18071338.
Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms and prolonging survival. Currently, available therapeutic options are surgery, radiation, chemotherapy, immunotherapy, and use of targeted drugs. However, thus far, therapies targeting cancer-associated molecular pathways have not given satisfactory results; this is due in part to the rapid upregulation of compensatory alternative pathways as well as dense desmoplastic reaction. In this review, we summarize currently available therapies and clinical trials, directed towards a plethora of pathways and components dysregulated during PDAC carcinogenesis. Emerging trends towards targeted therapies as the most promising approach will also be discussed.
胰腺导管腺癌(PDAC)占胰腺癌的90%,是全球癌症相关死亡的第四大主要原因。由于基因突变的广泛异质性和致密的基质环境,PDAC属于化疗耐药性最强的癌症之一。大多数现有治疗方法都是姑息性的,目的是缓解疾病相关症状并延长生存期。目前,可用的治疗选择包括手术、放疗、化疗、免疫疗法和使用靶向药物。然而,迄今为止,针对癌症相关分子途径的疗法尚未取得令人满意的结果;这部分是由于补偿性替代途径的快速上调以及致密的促纤维增生反应。在本综述中,我们总结了目前可用的疗法和临床试验,这些疗法针对PDAC致癌过程中失调的众多途径和成分。还将讨论作为最有前景方法的靶向治疗的新趋势。