a Northwell Health Cancer Institute , Donald and Barbara Zucker School of Medicine at Hofstra/Northwell , Lake Success , NY , USA.
b Cold Spring Harbor Laboratory , Cold Spring Harbor , NY , USA.
Expert Opin Drug Metab Toxicol. 2019 Jul;15(7):541-552. doi: 10.1080/17425255.2019.1637417. Epub 2019 Jul 5.
: Pancreatic cancer (PC) remains a disease with a dismal prognosis. Despite accounting for only 3% of cancer diagnosis, 7% of all cancer deaths in the United States are from PC. This is explained by many being diagnosed with late-stage disease and the cancer's resistance to chemotherapy. Since 1996 there have only been two upfront regimens found to be superior to gemcitabine, FOLFIRINOX (5-fluorouracil/leucovorin and oxaliplatin) and gemcitabine plus nab-paclitaxel. : Clinical pharmacology of newer agents that are either approved or being investigated in the management of PC. Knowledge of their pharmacokinetics, pharmacodynamics, and pharmacogenetics can be used to predict outcomes for specific patient populations. Drugs discussed include nanoliposomal irinotecan, pegvorhyaluronidase alfa, poly (ADP-ribose) polymerase enzyme inhibitors, larotrectinib, and napabucasin. : PC is a heterogeneous disease and outcomes are likely to improve as better predictive models of an individual's response to different therapies are developed. This may be best accomplished through phase 0 studies and the use of tumor organoid models grown from initial biopsies or resected tissue. The genetic and physical makeup of the tumor as well as the functional characterization in patient-derived organoids (PDOs), can help guide which agents may be most efficacious or toxic.
胰腺癌（PC）仍然是一种预后不良的疾病。尽管在美国，PC 仅占癌症诊断的 3%，但所有癌症死亡的 7%是由 PC 引起的。这是由于许多患者被诊断为晚期疾病，而且该癌症对化疗有抵抗力。自 1996 年以来，只有两种一线治疗方案被发现优于吉西他滨，即 FOLFIRINOX（5-氟尿嘧啶/亚叶酸和奥沙利铂）和吉西他滨加 nab-紫杉醇。
讨论的药物包括纳米脂质体伊立替康、聚乙二醇化尿酸酶、多聚（ADP-核糖）聚合酶抑制剂、拉罗替尼和那帕布辛。PC 是一种异质性疾病，随着更好地预测个体对不同治疗方法的反应的模型的开发，其预后可能会得到改善。这可能通过 0 期研究和使用从初始活检或切除组织中生长的肿瘤类器官模型来实现。肿瘤的遗传和物理结构以及患者来源的类器官（PDO）中的功能特征，可以帮助指导哪些药物可能最有效或最具毒性。
