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Published on: November 23, 2014
Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy
1Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 670 Albany Street, Boston, MA 02118, USA.
Abstract:
Metastasis is the primary cause of cancer-related mortality. Cancer cells primarily metastasize via blood and lymphatic vessels to colonize lymph nodes and distant organs, leading to worse prognosis. Thus, strategies to limit blood and lymphatic spread of cancer have been a focal point of cancer research for several decades. Resistance to FDA-approved anti-angiogenic therapies designed to limit blood vessel growth has emerged as a significant clinical challenge. However, there are no FDA-approved drugs that target tumor lymphangiogenesis, despite the consequences of metastasis through the lymphatic system. This review highlights several of the key resistance mechanisms to anti-angiogenic therapy and potential challenges facing anti-lymphangiogenic therapy. Blood and lymphatic vessels are more than just conduits for nutrient, fluid, and cancer cell transport. Recent studies have elucidated how these vasculatures often regulate immune responses. Vessels that are abnormal or compromised by tumor cells can lead to immunosuppression. Therapies designed to improve lymphatic vessel function while limiting metastasis may represent a viable approach to enhance immunotherapy and limit cancer progression.
Insights
Strategies to limit cancer metastasis are crucial. This review explores resistance to anti-angiogenic therapies and challenges in anti-lymphangiogenic treatments, suggesting improved lymphatic vessel function could enhance immunotherapy.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Metastasis, driven by cancer cell spread through blood and lymphatic vessels, is the leading cause of cancer mortality.
- Resistance to anti-angiogenic therapies targeting blood vessels is a major clinical hurdle.
- No FDA-approved drugs currently target tumor lymphangiogenesis, despite its role in metastasis.
Purpose of the Study:
- To review key resistance mechanisms to anti-angiogenic therapy.
- To identify potential challenges for anti-lymphangiogenic therapy.
- To explore the role of vasculature in immune regulation and its therapeutic implications.
Main Methods:
- Literature review of current research on cancer metastasis and therapeutic resistance.
- Analysis of mechanisms underlying resistance to anti-angiogenic treatments.
- Exploration of the interplay between tumor vasculature, immune response, and metastasis.
Main Results:
- Identified significant resistance mechanisms to existing anti-angiogenic therapies.
- Highlighted challenges and limitations in developing anti-lymphangiogenic therapies.
- Emphasized the immune-regulatory functions of blood and lymphatic vessels in the tumor microenvironment.
Conclusions:
- Overcoming resistance to anti-angiogenic therapies is critical for improving cancer treatment outcomes.
- Targeting lymphangiogenesis presents unique challenges but holds therapeutic potential.
- Enhancing lymphatic vessel function alongside metastasis limitation may synergize with immunotherapy to improve cancer progression and patient prognosis.
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