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

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....

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Published in:Biochimica et biophysica acta. Reviews on cancer 2023-09, Vol.1878 (5), p.188958-188958, Article 188958
Main Authors: An, Yan-Fei, Pu, Ning, Jia, Jin-Bin, Wang, Wen-Quan, Liu, Liang
Format: Article
Language:English
Subjects:
Angiogenesis
Anti-angiogenic therapy
Humans
Immunotherapy
Neovascularization, Pathologic - drug therapy
Pancreatic cancer
Pancreatic Neoplasms
Pancreatic Neoplasms - pathology
TME reprogramming
Tumor Microenvironment
Vascular remodeling
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Summary: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.
ISSN:0304-419X
1879-2561
DOI:10.1016/j.bbcan.2023.188958