Malik Shivani, Westcott Jill M, Brekken Rolf A, Burrows Francis J
Kura Oncology, Inc., San Diego, CA 92130, USA.
Division of Surgical Oncology, Department of Surgery, and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cancers (Basel). 2021 Dec 24;14(1):86. doi: 10.3390/cancers14010086.
Pancreatic ductal adenocarcinoma (PDAC) is a disease with limited therapeutic options and dismal long-term survival. The unique tumor environment of PDAC, consisting of desmoplastic stroma, immune suppressive cells, and activated fibroblasts, contributes to its resistance to therapy. Activated fibroblasts (cancer-associated fibroblasts and pancreatic stellate cells) secrete chemokines and growth factors that support PDAC growth, spread, chemoresistance, and immune evasion. In this review, we focus on one such chemokine, CXCL12, secreted by the cancer-associated fibroblasts and discuss its contribution to several of the classical hallmarks of PDAC and other tumors. We review the various therapeutic approaches in development to target CXCL12 signaling in PDAC. Finally, we propose an unconventional use of tipifarnib, a farnesyl transferase inhibitor, to inhibit CXCL12 production in PDAC.
胰腺导管腺癌（PDAC）是一种治疗选择有限且长期生存率极低的疾病。PDAC独特的肿瘤环境，包括促结缔组织增生性基质、免疫抑制细胞和活化的成纤维细胞，导致其对治疗产生抗性。活化的成纤维细胞（癌症相关成纤维细胞和胰腺星状细胞）分泌支持PDAC生长、扩散、化疗耐药性和免疫逃逸的趋化因子和生长因子。在本综述中，我们重点关注癌症相关成纤维细胞分泌的一种此类趋化因子CXCL12，并讨论其对PDAC和其他肿瘤的几种经典特征的作用。我们综述了目前正在开发的针对PDAC中CXCL12信号传导的各种治疗方法。最后，我们提出一种法尼基转移酶抑制剂替匹法尼的非常规用途，以抑制PDAC中CXCL12的产生。
