Molecular biology of targeting lymphangiogenesis in cancer: therapeutic strategies and future promise

Lymphangiogenesis is considered the rate-limiting step for tumor lymph node (LN) metastasis by sprouting the new lymphatic network from preexisting lymphatic vessels to favor the invasion and entry of cancer cells into the lymphatic system. Over the past decade, numerous studies have investigated the cellular roles and molecular mechanisms of lymphangiogenesis in cancers, and corresponding molecular control strategies targeting lymphangiogenesis to treat LN metastatic cancers have been developed. Nevertheless, due to the crucial role of lymphatic vessels in the infiltration of immune cells and immune activation in cancers, there have been several diverse findings regarding the biological roles and strategies of targeting tumor lymphangiogenesis as cancer immunotherapy has emerged and rapidly developed. Herein, we summarize the progress in characterizing the molecular mechanisms and therapeutic strategies involved in tumor lymphangiogenesis and highlight the potential of targeting lymphangiogenesis in combination with immunotherapy for the treatment of cancer, providing opportunities to improve the efficacy of targeting lymphangiogenesis to prevent cancer metastasis.