Interstitial fluid pressure as an obstacle in treatment of solid tumors

Over the past decades a development of different anticancer drugs has increased and brought many progressive agents that showed high level of efficiency in in vitro conditions. Unfortunately these drugs failed in solid tumor treatment in in vivo conditions because of inadequate uptake and nonoptimal distribution in tumors. Although tumors have higher permeability and hydraulic conductivity of the vessels than normal tissue, the extravasation of the drug molecules from vessels into the tumor interstitium is reduced due to elevated interstitial fluid pressure (IFP). This property also impedes the transport of the molecules through the interstitial space. Furthermore, IFP is uniformly high in the center of the tumor and declines to the value of the normal tissue at the rim of the tumor. Though, IFP gradient causes fluid flow which "washes" drugs out of the tumor to its periphery where it is reabsorbed by the lymphatic system or normal vasculature. Measurements of tumor IFP demonstrated that its values can reach 2600 Pa up to 6600 Pa whereas in the normal tissue it is below the atmospheric pressure (from -133 Pa to -798 Pa in s.c. and approximately -346 Pa in muscle). The most frequently used methods for installl and direct IFP measurement are: wick-in-needle technique (WIN) and micropuncture technique (MP). Since the reduction of the elevated tumor IFP could facilitate drug uptake and anti-tumor treatment, many approaches have been tested. In present paper we represent the results of two physical (hyperthermia, radiation) and one chemical (vasoactive agents) approach that other authors used for IFP reduction.