The role of angiogenesis in melanoma: Clinical treatments and future expectations

Abstract

The incidence of melanoma has increased rapidly over the past few decades, with mortality accounting for more than 75% of all skin cancers. The high metastatic potential of Melanoma is an essential factor in its high mortality. Vascular angiogenic system has been proved to be crucial for the metastasis of melanoma. An in-depth understanding of angiogenesis will be of great benefit to melanoma treatment and may promote the development of melanoma therapies. This review summarizes the recent advances and challenges of anti-angiogenic agents, including monoclonal antibodies, tyrosine kinase inhibitors, human recombinant Endostatin, and traditional Chinese herbal medicine. We hope to provide a better understanding of the mechanisms, clinical research progress, and future research directions of melanoma.

CDC42 Inhibitors Alter Patterns of Vessel Arborization in Skin and Tumors in vivo

“…Microfluidic device fabrication and loading have been previously described (5–6). In summary, a custom polyurethane master mold was created using a two-part polyurethane liquid plastic (Smooth Cast 310, Smooth-On Inc.).…”

“…The tumor vasculature is characterized by large tortuous vessels with leaky basement membranes and unperfused voids ( 16, 17 ). While longitudinal imaging approaches have provided structural insight into how vessels develop or repair after injury ( 5, 18 ), this information alone has not identified better therapies for conditions characterized by pathologic angiogenesis, such as inherited skin vascular anomalies ( 19, 20 ) or melanoma tumors ( 6 ), where existing anti-angiogenic therapies are many times toxic or only minimally effective ( 21 ).…”

“…Generation of the capillary plexus depends on the regression of existing vessels during the maturation process, and similar types of vessel regression are observed in conditions where the adult vasculature needs to be remodeled ( 5 ). All tumors, particularly those that arise in the epidermis that lack their own vasculature, are dependent on the ability to induce the growth of vessels around them ( 6–8 ). Tumors rapidly accelerate angiogenesis by producing a cornucopia of angiogenesis-promoting factors, inducing a haphazard, tortuous vessel tree that is unable to deliver nutrients evenly to the tumor ( 9, 10 ).…”

“…Melanoma tumors are minimally responsive to anti-angiogenesis agents(6). Tumor vessels can rapidly regrow after the cessation of VEGF-targeted therapies(64,65,67), and VEGF inhibitors seem to affect the blood vessels in the periphery but not the central part of the tumor(17).…”

Multidisciplinary approach and treatment of acral and mucosal melanoma

“…Based on the results discussed above ( 16 , 100 , 101 , 103 , 104 , 111 ), these maybe alternative therapeutic options for patients harboring KIT mutations. Combination therapies have shown the most promise ( 124 , 125 ). Ongoing clinical trials are evaluating the efficacy of several tyrosine kinase inhibitors in AM and MM, including NCT03991975, NCT00788775 and NCT03955354.…”