Chapter 5 - Challenges and future directions

Abstract

Cancer is a worldwide health issue, and there is an urgent need to identify additional effective, noninvasive biomarkers for early diagnosis, prognosis, and therapeutic targeting based on individual patient characteristics. Currently, cancer patients are categorized based on the site and tissue of origin of the disease. However, it is becoming increasingly clear that the biological barriers and heterogeneity seen in tumors and patients calls for more targeted therapy over conventional cancer treatment methods. Development of targeted cargo delivery or active pharmaceutical agent ingredients for specific disease pathologies—that is, the process of drug discovery—has been instrumental in generating new lead molecules for a plethora of disease conditions. While early drugs were nearsighted by serendipity, discovery has been expedited by the introduction of novel discovery tools including high-throughput screening, structure-activity relationships, combinatorial chemistry, computer-aided drug design, and artificial intelligence. Although the process of lead identification is robust, drugs often fail in later stages of development, often because of safety and efficacy concerns that fundamentally arise from high accumulation in off-target organs or poor accumulation in target organs. This has been a major block in the translation of potent drug candidates, which inherently possess excellent potential but fail to demonstrate significant clinical impact owing to dose-related toxicities or dose-limited efficacies resulting from off-target effects. Drug delivery technologies hold the potential to address this limitation and have emerged in parallel to the drug discovery process. Over the years, drug delivery research has offered multiple approaches to target drugs, including local therapies such as topical formulations and physical devices. Local therapies offer the simplest means of targeting; however, they are not practical when disease sites are hard to reach. In addition, nanoparticles have been developed to target therapies to specific tissues. Modulation of physicochemical properties such as size and charge could improve nanoparticles’ targeting to specific tissues; however, nanoparticles face biological barriers that impede their targeting capabilities. In this chapter, some of the challenges in targeted delivery are discussed, and then several relatively new approaches that may be used to facilitate imaging for cancer detection and treatment are described.