COINS Seminar #6
Current paradigm of therapeutic cancer nanomedicine and its
prospective: A gap between preclinical and clinical Outcomes
You Han Bae, PhD

Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah

Date: Friday, December 19, 2014 Time: 17:30～18:30
Venue: Room #56, Engineering building #5,
The University of Tokyo—Abstract—

The current paradigm of cancer nanomedicines relies heavily on long circulation time,enhanced permeability and retention (EPR) effect, and cell specific interactions.
EPR effect is the single most cited term in literature from the past decades covering cancer
nanomedicine for therapy and diagnosis. It has been supported by high accumulation in thetumor of intravenously introduced nanoparticles. However, the degree of accumulation
widely fluctuates in animal tumor models and clinical tumors. Although EPR effect may exist, its nature is not fully
understood and there is no practical way to predict its extent, especially in clinical settings, for any given solid tumor.
This presentation discusses the heterogeneity and potential uncertainty of the EPR effect.
The concept of a “Magic Bullet” implicitly presumed that soluble or nanosized drug carriers possessed a homing
function to the targeted disease sites, solid tumors, because of their design for specific cancer cell interaction. This
paradigm continues till now and intensive researches have been being conducted for the last three decades in thisparadigm which has seemingly been proven in in vitro tests and small animal cancer models by xenografting humantumors or genetically engineering. However, the approach has not yet proven its efficacy in clinical settings. It is known
that the accumulation of the drug carriers at a target tumor, which is limited to a small fraction of total dose, is governed
by various physiological and physicochemical factors, such as vascular permeability and interstitial pressure, rather thanspecific secondary interactions.
Moreover, cancer cells and malignant tumors are not fully understood, and new discoveries continue to decipher new
aspects of tumor origination, physiology, and cell biology. A tumor is not merely a large, isolated mass of identicalcancer cells. Genetic instability contributes to the ability of cancer cells to survive, proliferate, and disseminate, but thissame instability also leads to tumor cell heterogeneity and diversified epigenetic regulation. In addition, tumors are now
gaining recognition as a sort of organized tissue/organ with stromal cells ostensibly recruited from the host body.
Accordingly the current paradigm of EPR effect and targeted drug delivery which was developed based on an overly
simplified tumor models may require modification or a shift to reflect at least current understanding of tumor
physiology and cancer biology, particularly tumor heterogeneity. In addition due to the poor predictive power of current preclinical models for clinical outcome,we may need to review how closely current in vitro and in vivo models do resemble clinical tumors.
＊Organizer: Center of Innovation (COI program)
Kensuke Osada, Associate Professor, Graduate School of Engineering, The University of Tokyo＊Cooperation: International Core Research Center for NanoBio (C2CNB), The University of Tokyo
Grants for Excellent Graduate Schools "Medical System Innovation through Multidisciplinary
Integration”＊For Further Information Contact: COINS Research Support OfficeE-mail: jimukyoku@coins.t.u-tokyo.ac.jp Web: http://www.kawasaki-net.ne.jp/coins/