David A. Tuveson

David Tuveson is one of the foremost authorities on pancreatic ductal adenocarcinoma (PDAC), serving as Director of the Cancer Center at Cold Spring Harbor Laboratory and Roy J. Zuckerberg Professor of Cancer Research. His laboratory has fundamentally advanced the understanding of KRAS oncogene biology in pancreatic cancer and pioneered the use of patient-derived organoids as preclinical models for drug testing and personalized medicine. Tuveson's early work established genetically engineered mouse models of pancreatic cancer — most notably the KPC model (KrasG12D/+; Trp53R172H/+; Pdx-1-Cre), which recapitulates the clinical and histological features of human PDAC with remarkable fidelity. The KPC model became an indispensable platform for understanding disease progression from PanIN precursors to invasive carcinoma and for evaluating therapeutic strategies in an immunologically intact host. This work revealed that the dense desmoplastic stroma surrounding pancreatic tumors constitutes a major barrier to drug delivery and immune infiltration, reorienting the field's approach to stroma-targeting strategies. In 2015, Tuveson's laboratory reported one of the first protocols for generating human pancreatic ductal organoids from patient biopsy material, enabling the expansion and maintenance of primary tumor tissue in three-dimensional culture systems that preserve key genetic and histological features of the original tumor. These patient-derived organoids have been used to perform drug sensitivity profiling that correlates with clinical responses, offering a path toward functional precision medicine in PDAC. Tuveson has also made foundational contributions to understanding KRAS biology in pancreatic cancer. His group demonstrated that KRAS drives a metabolic reprogramming in pancreatic cancer cells — including upregulation of macropinocytosis for amino acid scavenging — and that tumor cells exhibit distinct dependencies on KRAS effector pathways compared to normal cells, with implications for targeted therapy development. His work on KRAS G12D direct inhibitors has been a focal point as the field moves toward targeting the most common PDAC mutation directly. As a leader in the Pancreatic Cancer Collective and multiple NCI-funded research programs, Tuveson has shaped national strategy for pancreatic cancer research and fostered translational collaboration between basic scientists and oncologists.

David Tuveson 是胰腺导管腺癌（PDAC）领域最权威的专家之一，担任冷泉港实验室癌症中心主任。他的实验室从根本上推进了对胰腺癌KRAS癌基因生物学的理解，并率先将患者来源的类器官用于药物测试和个性化医学的临床前模型。 Tuveson 早期工作建立了胰腺癌基因工程小鼠模型（最著名的KPC模型），能高度还原人类PDAC的临床和组织学特征，揭示了肿瘤周围的致密促纤维增生性间质是药物递送和免疫浸润的主要障碍。2015年，他的实验室报道了从患者活检材料中生成人胰腺导管类器官的方法，实现了原代肿瘤组织的体外扩增，为功能性精准医学奠定基础。他在KRAS代谢重编程和KRAS G12D直接抑制剂领域的工作为靶向治疗开发提供了重要方向。