Combining two strategies to improve perfusion and drug delivery in solid tumors

摘要: Blood perfusion in tumors can be significantly lower than that the surrounding normal tissue owing to leakiness and/or compression of tumor blood vessels. Impaired reduces oxygen supply and results a hypoxic microenvironment. Hypoxia promotes progression immunosuppression, enhances invasive metastatic potential cancer cells. Furthermore, poor lowers delivery systemically administered drugs. Therapeutic strategies improve include reduction vascular permeability by normalization decompression alleviating physical forces (solid stress) inside tumors. Both have shown promise, but guidelines on how use these optimally are lacking. To this end, we developed mathematical model guide optimal strategies. The accounts for vascular, transvascular, interstitial fluid drug transport as well diameter Model simulations reveal an region when vessels uncompressed, not very leaky. Within region, intratumoral distribution drugs is optimized, particularly 10 nm or smaller low binding affinity. Therefore, treatments should modify vessel such optimal. Vascular more effective hyperpermeable largely uncompressed (e.g., glioblastomas), whereas solid stress alleviation beneficial compressed less-permeable pancreatic ductal adenocarcinomas). In case with subset mammary carcinomas), two need combined improved treatment outcomes.