Recent progress in the molecular understanding of cancer has enabled us to identify new and critical molecular targets for cancer treatments. Translational research (TR) covers a wide range of medical research - from bench to bed. The promotion of TR is essential for the development of novel agents for cancer, and began as national projects in 2005 under the Third 10-year Research Promotion for Innovative Therapies against Cancers.
However, there remain many financial, legal, ethical, and organizational barriers to the development of TR. Compared with Western countries, TR in Japan is too frail to constitute the basis for the (pre-) clinical trial in rapidity, safety and reliability. To flower the TR more, we have to continue to pursue TR as a national policy. Here, we discuss about the problem which now confronts us on TR, and consider how TR should be developed further.

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The core of translational research (TR) is the idea of "bench-to-bedside", establishing achievements of basic research through clinical applications. TR revolutionizes the current drug development process in Japan, encouraging faster and more cost-effective drug development, transforming the R&D organizations, and fostering bio-venture companies. TR is a powerful process in reviving the international competitiveness of domestic pharmaceutical companies.

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Understanding of the relationship of oral absorption and oral bioavailability (BA) of potential drug candidates between animals and humans is important in drug discovery and development. Despite the similarities in monkeys and humans, marked differences have been found in oral BA for many drugs. Because BA values determine the therapeutic potential of a drug, caution should be exercised in extrapolating data obtained in animals, especially in monkeys as it may not predict that in humans. There have been many improvements in predicting human pharmacokinetics, which are determined by functions of metabolic enzymes and transporters, based on a combination of animal, in vitro, and in silico (e.g., physiologically-based pharmacokinetic) models, but failures still occur.
Microdosing studies in humans potentially have an important place in the drug development process inasmuch as they can offer an early determination of the pharmacokinetic properties of a compound and thus assist in the selection of those drug candidates that possess optimal disposition properties for further evaluation in the clinic. This strategy allows early evaluation of systemic clearance, oral bioavailability, and excretion ratio into urine as well as sources of intersubject variability and questions of specific metabolite formation.

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In the process of drug development, animal experiments are inevitable but may not reflect accurately the human conditions due to species difference in drug disposition, especially metabolism. In this paper, species differences in drug metabolizing enzymes and a method to predict human pharmacokinetics are explained.

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The Developmental Therapeutics Program (DTP), which initiated by the Division of Cancer Treatment & Diagnosis (DCTD) of National Cancer Institute (NCI) in U.S.A., supports the various researches to develop new therapeutic agents for cancer. DTP also has the Rapid Access to Intervention Development (RAID) program to assist translation to the clinic of novel anticancer therapeutic interventions arising in the academic community. NCI staffs directly interact with the investigators and perform the RAID-approved tasks. RAID is a program designed to facilitate translational researches by making NCI resources including experienced staffs available to the academic research community for the preclinical development of drugs and biologics.

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The purpose of translational research(TR) is to integrate the information from basic research into clinical study and vice versa. The ultimate goal of TR is to bring a new remedy in clinics with reasonable fashion. In this chapter, example of several TRs regarding anticancer agents incorporated micelles are introduced and several problematic issues regarding investigational new drug application for DDS are discussed.

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Serious stagnation and low productivity in new drug discovery and development have been raised an alarm how the pharmaceutical industry can explore appropriate drug candidates and conduct efficient development as well as preventing drop-out at the later clinical stage. For this purpose, we must reconsider several empirical and stereotypical programs so far used in clinical development. Instead, the human based exploratory clinical study such as single micro dosing PK study campaigned by both US and European regulatory agencies might be one of powerful tools to ascertain the possibility "to go" or "not to go" at the earlier stage of drug development.
In order to improve traditionally insufficient subject enrollments only in domestic clinical trials, participation in multinational clinical trials will make possible an adequate evaluation of drug safety and efficacy through systematic comparison with foreign data. Further efforts should be paid to establish an infrastructure and circumstance to achieve this kind of clinical trials in Japan soon. We should also learn about how to manage the provisions of Japan own by referring not only clinically forward US and European countries but also Asian.
The ICH E2E-guided proactive post-marketing surveillances and clinical trials after approval might be important for understanding the details without consuming too much time as well as money at the R&D stages.

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