James H. Doroshow, M.D., Director, DCTD: I think that if you compare the time from my first introduction to the Developmental Therapeutics Program, which was 30 years ago when I first came to the NIH, to today, the major, major improvement in our overall understanding of what causes cancer and thus the development of a whole series of rational new targets for eliminating the growth of cancer cells has got to be the principle discovery over the past 30 years that has allowed the development and consideration of development of a whole range of new therapeutic approaches that would have been impossible 30 years ago.

Anna D. Barker, Ph.D., Deputy Director for Advanced Technologies and Strategic Partnerships, NCI: To really meet our challenge goal of eliminating suffering and death due to cancer in a decade is obviously a major challenge. It's not so much a goal as it is a challenge to our investigators and to all sectors working in cancer research to actually really redouble their efforts to apply what we know. And if we could apply what we know, we could actually change an awful lot of what's going on in terms of morbidity and mortality from cancer.

Doroshow: And so we have to meet those challenges by developing a more integrated, more timely development process; by interacting with the extramural community in such a way to bring more molecules forward more quickly; and to utilize all of the resources of the entire NIH community to allow drug development to proceed in the most effective fashion.

Michael Grever, M.D., Former Associate Director, DTP: Molecular targeting as a concept is very attractive. It is rational, it is hopefully selective. It certainly is the wave of the future. The important aspect of finding an important targeting of a malignant cell or an important pathway enables us to have a better understanding of the biology and the susceptibility that we can approach to try to eradicate drug resistant cells.

Barker: We believe that the future of drug development is going to involve thousands of targets.

Michael Boyd, Former Associate Director, DTP: Targeted drug discovery, by definition, means that you're going to be focusing on targeted subsets of human patient populations that are smaller than are typically appealing as an area for drug development of the big pharmaceutical industries.

Barker: No one, no one organization, no one sector can actually move these kind of new interventions from discovery into patients. It takes the private sector, the academic sector, the non-profit sector to really work together with the regulators to make this happen.

Grever: We're now entering a period where pharmacodynamic or pharmacogenomic measures are also contributing to the development of these drugs.

Grever: Pharmacodynamic studies actually validate whether or not the drug hits the target that you thought was important. What we have found is the differences in various sub-populations of patients with respect to drug metabolism can have a major impact on whether or not a drug is going to work or not.

Barker: We're hoping in the future that we can use some of these new technologies to know way, way up, early in the process whether or not things are going to be safe and more specifically if they're going to be targeted to specific genetic defects in cells.

Grever: So we need to incorporate concepts of pharmakinetics and pharmacogenomics into the drug development process. In the future we hope that patients will be profiled and so we will know what specific metabolic pathways are going to be more likely to be effective in treating a cancer.

Boyd: The importance of the NCI's anti-cancer drug development program and any other government sponsored program is becoming greater and greater as the perceived risk and as the economics look less favorable to the for-profit 19pharmaceutical industry, particularly at the early stages when the risk is highest and the investment is great.

Doroshow: Recently there has been a shift in the regulatory environment that will allow in the very near future very early studies of relatively non-toxic drugs to be performed more quickly in patients.

Doroshow: One of our goals is to utilize this regulatory shift, utilizing the infrastructure that the Developmental Therapeutics Program has, to bring several new agents more quickly to clinical trial.

Barker: Ultimately we are all about bringing new advances to patients. That's why I'm here, that's why everyone at the Cancer Institute comes to work every day.

Doroshow: I think that what you can continue to expect for the future are a series of new drugs that are poised to be approved that are conveniently delivered; that is given by mouth, that have very modest side effect profiles, that control cancer growth by novel mechanisms, and that will for the first time control a series of kinds of cancers that standard chemotherapies have been really ineffective at controlling.