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The reduction of tumor-draining lymphatic vessel contraction could lead to the elevation of interstitial fluid pressure in primary tumor sites (119, 120), which might drive cancer cells to migrate toward functional lymphatic vessels that are mainly positioned in the tumor margin (68)

As the primary factors for the reduced anticancer effect 1) the reduced delivery and uptake of the anticancer agent, 2) the need for the conversion of molecular oxygen (O 2 ) into reactive oxygen species (ROS), 3) the preferred therapeutic effect against highly proliferating cells, which is reduced under hypoxic conditions, or 4) adaptation of the cancer cells by promoting cell survival and upregulating certain resistance pathways, has been suggested 1,2,3,4,5