Clinical Cancer Research Vol. 10, 8129, December 15, 2004
© 2004 American Association for Cancer Research
Moving Discovery into Clinical Practice
John Mendelsohn, Editor-in-Chief
Clinical Cancer Research
Ten years ago I was offered the privilege of serving as founding Editor-in-Chief of AACR’s new journal, Clinical Cancer Research. I am grateful that I have had this opportunity. Our goal was, and is, to be the leader in "publishing articles describing clinical research on the cellular and molecular characterization, prevention, diagnosis and therapy of human cancer. [The] focus is on innovative clinical research and translational research that bridges the laboratory and the clinic."
The rapid growth that Clinical Cancer Research has experienced in both submissions and readership is due to increased investigator interest in applications of science to disease, and to the tremendous progress in new technologies for studying genetic and molecular mechanisms in the laboratory and in the patient.
The pages of this journal have documented hundreds of qualitative and quantitative changes in the genes and proteins in cancer cells. The relevance of these observations has been demonstrated primarily by correlations with outcomes and responses to therapy.
Hundreds of articles have also reported results of targeted clinical and preclinical studies on therapies that act by blocking or correcting the results of abnormalities in genes and proteins. Notable successes have been achieved with agents that block tyrosine kinases, as well as some other targets.
How can we speed up the timeline for bringing this new knowledge into clinical practice? Can we more rapidly convert statistically significant correlations between molecular abnormalities and clinical outcomes into validated molecular markers that are useful in clinical practice? Can we speed up the clinical validation of therapies that target abnormal genes and proteins? Here are some suggestions:
- Because new targeted therapies act on human cells in ways that are often not predictable from animal studies, we must bring them into the clinic earlier, with proper safeguards for toxicity and with thorough pharmacodynamic (mechanistic) and pharmacokinetic studies on each patient to identify the biologically effective dose and optimal schedule as soon as possible.
- New statistical techniques should be used to move new therapies seamlessly through phase I-II-III trials, building on and incorporating prior data at each step.
- Guidelines should be developed by researchers and the Food and Drug Administration to allow testing of new therapies in early-stage rather than end-stage disease and to enable new agents that may be active against only a minority of cancer patients to be used earlier in combinations that allow targeting of more than a single gene or protein abnormality.
- Pharmaceutical companies, the National Cancer Institute, and payers should fund far more research to discover and validate molecular markers in the tumor and in the patient, which will identify patients most likely to respond to a particular treatment and more rapidly identify the responders.
- We need new mechanisms of grant and contract funding that support large-scale collaborations between laboratory researchers and clinical investigators, who may come from multiple institutions and companies.
- Universities must place greater emphasis on nurturing, incentivizing, and promoting faculty whose research is clinical and collaborative. There must be greater emphasis on other "gold standards" for academic promotion and tenure besides R01 funding to a principal investigator to reward researchers who participate in collaborative clinical trials, and researchers must be given "protected time" for clinical investigations similar to that provided to laboratory scientists.
- Physicians must agree to collect clinical information and research data in a standardized format that can be shared with all interested parties by simple electronic transfer. In the future, uniform electronic medical records could be mined for correlations of molecular and diagnostic information with responses to therapy and outcomes, so that each patient becomes a source of research data.
- Physicians, advocates, and survivors should offer encouragement and education to recruit patients to participate in clinical trials in far greater numbers.
- The current process for designing clinical trials involves too much time negotiating and protecting interests. We need to streamline the cascade of reviews and approvals required for initiating new protocols and deal with the log jam of intellectual property claims that can slow down both preclinical studies and clinical trials.
- Off-label use of anticancer agents in new situations must be encouraged and reimbursed, if incorporated into clinical trials that will determine efficacy.
- More research is needed on how to motivate changes in lifestyles, particularly in the areas of tobacco use and nicotine dependence. Ultimately, individuals must take greater responsibility and accountability for making use of existing knowledge that will reduce cancer incidence or improve cure rates through earlier detection.
It is time for academic, industrial, and federal researchers to take the lead in working to implement these and other changes in how we do things, to enable the fruits of a magnificent few decades of accomplishments in cancer research to be converted into effective diagnostic, therapeutic, and preventive interventions for the benefit of patients.
