The Future of Lymphedema: Potential Therapeutic Targets for Treatment

Abstract

Purpose of Review This review aims to summarize the current knowledge regarding the pharmacological interventions studied in both experimental and clinical trials for secondary lymphedema. Recent Findings Lymphedema is a progressive disease that results in tissue swelling, pain, and functional disability. The most common cause of secondary lymphedema in developed countries is an iatrogenic injury to the lymphatic system during cancer treatment. Despite its high incidence and severe sequelae, lymphedema is usually treated with palliative options such as compression and physical therapy. However, recent studies on the pathophysiology of lymphedema have explored pharmacological treatments in preclinical and early phase clinical trials. Summary Many potential treatment options for lymphedema have been explored throughout the past two decades including systemic agents and topical approaches to decrease the potential toxicity of systemic treatment. Treatment strategies including lymphangiogenic factors, anti-inflammatory agents, and anti-fibrotic therapies may be used independently or in conjunction with surgical approaches.

Advances in lymphedema: An under-recognized disease with a hopeful future for patients

“…There is now interest in exploring angiotensin-converting enzyme inhibitors as well. 116,122 The focus of this review is peripheral lymphedema but as more is understood about lymphatics, it is becoming clear that they play an integral role in a variety of disease states beyond peripheral lymphedema. 26 The role of lymphatics in cardiovascular disease has just recently been explored.…”

“…Lymphangiogenic factors have also been explored, particularly vascular endothelial growth factor C (VEGF-C), which regulates lymphatic vessel development and lymphatic endothelial cell proliferation and migration. 116 In animal models, recombinant VEGF-C increased lymphangiogenesis and improved lymphatic function, resulting in decreased edema. 117 More recently, VEGF-C has been incorporated into a nanofibrillar collagen scaffold (BioBridge TM Fibralign Corp, Union City, CA) utilized during physiologic surgeries to aid in the development of local lymphatics.…”

“…Antibodies targeting IL-4 and IL-13 were demonstrated to reduce Th2 cytokines and epidermal thickness. 116,121 Early data also suggest inhibition of the transforming growth factor beta-1 (TGF-β1) pathway may slow the fibrotic process and have shown promise in an animal model. There is now interest in exploring angiotensin-converting enzyme inhibitors as well.…”

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development

“…The recent understating of the dynamic adaptability of the lymphatic vessels, along with their crucial role in controlling various vital bodily functions, including physiological processes, inflammation, and fibrosis, has sparked significant interest in the creation of treatments aimed at the lymphatic system. Currently, clinical trials are currently investigating various lymphatic-specific treatments for lymphedema and malignancies (as reviewed in [ 79 , 80 , 81 , 82 , 83 ].…”

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention

“…Improved lymphatic contractility, swelling, T-cell infiltration, tissue fibrosis. Increased formation of lymphatic collateral vessels, decreased backflow (murine) [125][126][127].…”