Challenges and strategies in anti-cancer nanomedicine development: An industry perspective

Abstract

Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. We should evolve our nanomedicine development strategies to build the patient and disease into the line of sight from the outset. The success of small molecule targeted therapies has been significantly improved by employing a specific decision-making framework, such as AstraZeneca's 5R principle: right target/efficacy, right tissue/exposure, right safety, right patient, and right commercial potential. With appropriate investment and collaboration to generate a platform of evidence supporting the end clinical application, a similar framework can be established for enhancing nanomedicine translation and performance. Building informative data packages to answer these questions requires the following: (I) an improved understanding of the heterogeneity of clinical cancers and of the biological factors influencing the behaviour of nanomedicines in patient tumours; (II) a transition from formulation-driven research to disease-driven development; (III) the implementation of more relevant animal models and testing protocols; and (IV) the pre-selection of the patients most likely to respond to nanomedicine therapies. These challenges must be overcome to improve (the cost-effectiveness of) nanomedicine development and translation, and they are key to establishing superior therapies for patients.

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…These toxic excipients are often used in already existing marketed drug formulations, causing dose limiting toxicities of the drug. [106] Thus, nanoparticles can offer the advantages of improved drug tolerability and administration of high dose of anti-cancer drugs. For example, Cremophot™ is a dose-limiting toxic excipient commonly used in the currently marketed Taxol™ formulation.…”

“…Clinical nanomedicines like Abraxane™ and Genexol ® PM are able to achieve the administration of higher doses of paclitaxel in human patients due to the increased drug solubilization effect from the nanoparticles and by avoiding this toxic excipient. [106][107][108] In addition to the traditional small drug molecules, nanoparticles can also entrap large macromolecules, such as proteins, peptides, DNAs and RNAs to protect them from enzymatic degradation and to improve their stability during the transport and until they reach the active cancer tumor sites. [109,110] …”

“…[152] In addition, increasing evidence suggests that the EPR effect is heterogeneous and largely varies between patients and tumor types, particularly within the same patient and tumor over a period of time. [38,106,145] In a human tumor analysis study carried out in more than 200 patients with eight different types of cancer have shown large variation in tumor vasculatures, their location within the tumor, stroma and density, macrophage counts and distribution between patients and tumor types. [106] More importantly, marked difference was evidenced within the same patient or tumors.…”

“…[38,106,145] In a human tumor analysis study carried out in more than 200 patients with eight different types of cancer have shown large variation in tumor vasculatures, their location within the tumor, stroma and density, macrophage counts and distribution between patients and tumor types. [106] More importantly, marked difference was evidenced within the same patient or tumors. However, there has been only limited effect made to address the effect of EPR in improving the therapeutic efficacy of nanomedicines.…”

Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells

“…Nanotechnology is under intense scrutiny in the design of new medical protocols, as a significant improvement of diagnoses and therapy 1 , in particular of cancer and cardiovascular diseases, is expected from the application of nanosized drug delivery systems 2 . In this contest, liposomes, solid-lipid nanoparticles, and biodegradable polymeric nanoparticles are the most widely investigated systems.…”