The Achilles' Heel of Pancreatic Cancer: Targeting pancreatic cancer's unique immunologic characteristics and metabolic dependencies in clinical trials.
The Achilles' Heel of Pancreatic Cancer: Targeting pancreatic cancer's unique immunologic characteristics and metabolic dependencies in clinical trials.
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DOI：
10.1097/jp9.0000000000000052
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Oberstein PE
中科院分区：
文献类型：
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作者：
Siolas D;Morrissey C;Oberstein PE
胰腺导管腺癌（PDAC）死亡率很高，并且对多种癌症治疗都难以治愈。近年来，癌症治疗已从传统的细胞毒性化疗扩展到靶向药物和免疫疗法，并已在许多癌症中成功实施。尽管有大量的临床前研究，这些新疗法对 PDAC 的影响很小。然而，新出现的临床数据已取得成功，支持检查点抑制剂治疗和聚（ADP-核糖）聚合酶抑制剂靶向治疗对特定 PDAC 患者亚群的潜在作用。在本临床综述中，我们讨论了针对代谢途径以及普遍的肿瘤内免疫子集的最新临床前证据，并重点关注旨在测试 PDAC 中新药物的临床试验。将临床前发现转化为患者的挑战仍然很大，许多临床试验都产生了负面结果，但合作努力和对新型临床试验的重新关注使我们乐观地认为，我们将为 PDAC 患者找到更多选择，并改变这种致命疾病的结果。
Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and is notoriously refractory to multiple cancer treatments. In recent years, cancer therapy has expanded beyond traditional cytotoxic chemotherapy to targeted agents and immunotherapy which have been successfully implemented in many cancers. Despite robust pre-clinical research, these novel therapies have only had a small impact on PDAC. However, there have been successes with emerging clinical data supporting a potential role for checkpoint inhibitor therapy and targeted therapy with poly (ADP-ribose) polymerase inhibitors for select subsets of PDAC patients. In this clinical review, we discuss recent pre-clinical evidence for targeting metabolic pathways as well as prevalent intratumoral immune subsets, and focus on clinical trials designed to test novel agents in PDAC. The challenge of translating pre-clinical findings to patients remains substantial and many clinical trials yield negative results, but collaborative efforts and renewed focus on novel clinical trials have led to optimism that we will identify additional options for PDAC patients and change outcomes for this deadly disease.