Interstitial fluid pressure in tumors: therapeutic barrier and biomarker of angiogenesis

Abstract

Interstitial fluid pressure is elevated in virtually all solid malignant tumors as a result of abnormalities of the vasculature and interstitium. High interstitial fluid pressure is an independent predictor of disease recurrence in cervical cancer patients treated with radiotherapy, has been implicated as an important factor that impairs the delivery of chemotherapy to tumors and may influence the regulation and distribution of cytokines and growth factors. Targeted molecular treatments that inhibit angiogenesis or alter interstitial fluid dynamics also produce early reductions in interstitial fluid pressure. Reductions in interstitial fluid pressure due to anti-angiogenic treatment have been associated with improved therapeutic outcome in preclinical studies when these agents are combined with radiotherapy or conventional cytotoxic chemotherapy. Pretreatment interstitial fluid pressure and the change in pressure during treatment may provide important predictive information that in the future will be used to optimize therapy in individual patients.