Therapeutic advances targeting tumor angiogenesis in pancreatic cancer: Current dilemmas and future directions

Yan-Fei An; Ning Pu; Jin-Bin Jia; Wen-Quan Wang; Liang Liu

doi:10.1016/j.bbcan.2023.188958

Therapeutic advances targeting tumor angiogenesis in pancreatic cancer: Current dilemmas and future directions

Biochim Biophys Acta Rev Cancer. 2023 Sep;1878(5):188958. doi: 10.1016/j.bbcan.2023.188958. Epub 2023 Jul 24.

Authors

Yan-Fei An¹, Ning Pu², Jin-Bin Jia³, Wen-Quan Wang⁴, Liang Liu⁵

Affiliations

¹ Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Basic Medicine, Chang Zhi Medical College, Changzhi 046000，China; Department of Basic Medicine and Institute of Liver Diseases, Shan Xi Medical University, Taiyuan 030000, China.
² Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Basic Medicine and Institute of Liver Diseases, Shan Xi Medical University, Taiyuan 030000, China. Electronic address: jbjia@sxmu.edu.cn.
⁴ Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: wang.wenquan@zs-hospital.sh.cn.
⁵ Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: liu.liang@zs-hospital.sh.cn.

PMID: 37495194
DOI: 10.1016/j.bbcan.2023.188958

Abstract

Pancreatic cancer (PC) is one of the most lethal malignancies, which is generally resistant to various treatments. Tumor angiogenesis is deemed to be a pivotal rate-determining step for tumor growth and metastasis. Therefore, anti-angiogenetic therapy is a rational strategy to treat various cancers. However, numerous clinical trials on anti-angiogenetic therapies for PC are overwhelmingly disappointing. The unique characteristics of tumor blood vessels in PC, which are desperately lacking and highly compressed by the dense desmoplastic stroma, are reconsidered to explore some optimized strategies. In this review, we mainly focus on its specific characteristics of tumor blood vessels, discuss the current dilemmas of anti-angiogenic therapy in PC and their underlying mechanisms. Furthermore, we point out the future directions, including remodeling the abnormal vasculature or even reshaping the whole tumor microenvironment in which they are embedded to improve tumor microcirculation, and then create therapeutic vulnerabilities to the current available therapeutic strategies.

Keywords: Angiogenesis; Anti-angiogenic therapy; Pancreatic cancer; TME reprogramming; Vascular remodeling.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Immunotherapy
Neovascularization, Pathologic* / drug therapy
Pancreatic Neoplasms* / pathology
Tumor Microenvironment