Abstract
Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.
Highlights
Lymphangiogenesis is known as the formation of lymphatic vessels from pre-existing lymphatic vasculature
In recent years, during the concurrent studies that were carried out to detect approaches targeting lymphangiogenesis, multiple anti-angiogenic drugs exhibited inhibitory effects on lymphangiogenesis as well, advancing the progression in this field. According to their targets and modes of action, drugs targeting lymphangiogenesis can be categorized into several groups: 1) Antibody-based therapies [19], including monoclonal antibodies and some neutralizing antibodies or peptides directly targeting the VEGF-C/VEGFR-3 axis, which are currently tested in preclinical/clinical studies; the HGF/HGFR and newly identified Ang/Tie served as their targets
Tumor-induced lymphangiogenesis and therapeutics providing virtual management of lymphatic metastasis will continue their upward trend in advances based on the successive achievements
Summary
Lymphangiogenesis is known as the formation of lymphatic vessels from pre-existing lymphatic vasculature. The main discovered molecules that serve as potential targets are VEGFC, VEGF-D, VEGFR-2, VEGFR-3, HGF, and HGFRs. In earlier studies of the angiogenic process, many of these molecules have shown their promoting effects on angiogenesis; and until 2018, there have been 26 drugs approved by FDA for the anti-angiogenic therapy, with various indications [18].
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