Research Perspectives:

Targeting the invincible barrier for drug delivery in solid cancers: interstitial fluid pressure

Steven K. Libutti, Lawrence Tamarkin and Naris Nilubol _

PDF  |  HTML  |  How to cite  |  Press Release

Oncotarget. 2018; 9:35723-35725. https://doi.org/10.18632/oncotarget.26267

Metrics: PDF 1331 views  |   HTML 2260 views  |   ?  


Steven K. Libutti1, Lawrence Tamarkin1 and Naris Nilubol1

1 Department of Endocrine Oncology Branch, NCI/NIH, Bethesda, MD, USA

Correspondence to:

Naris Nilubol, email: [email protected]

Keywords: microenvironment; interstitial fluid pressure; drug delivery; tumor necrosis factor; nanomedicine

Received: September 26, 2018    Accepted: October 06, 2018    Published: November 06, 2018


Although a number of new systemic therapeutic options in patients with advanced solid cancers have emerged due to the improved knowledge of molecular dysregulation in cancers, the durable, long-term, objective responses infrequently occur. This editorial article highlights the major limitation of current systemic therapy due to an inefficient drug delivery. While several mechanisms contributing to cancer drug resistance have been described, the common key barrier among solid cancers is the unique tumor microenvironment that causes the high interstitial fluid pressure (IFP). We discussed the mechanism causing an elevated IFP and how it interferes with drug delivery. To target the high IFP, we demonstrated the novel approach using gold nanoparticle carrying recombinant human tumor necrosis factor (TNF), a vascular disrupting agent, that preferentially and specifically targets tumors while the systemic toxicity is markedly reduced. The addition of cytotoxic agent by either directly conjugating to the gold nanoparticle or by systemic administration following gold nanoparticle carrying TNF resulted in significantly reduced tumor burden and increased survival in multiple mouse models with primary and metastatic endocrine cancer and pancreatic ductal carcinoma. A clinical trial in patients with advanced solid cancers is warranted based on the promising results in preclinical studies.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 26267