Viewpoint: Shortening the Timeline for New Cancer Therapy

I write as a specialist in cancer, but the lessons learned in addressing this disease are widely applicable.

The "war on cancer" began in 1971 with bipartisan legislation that provided NIH funding for increased research on the cause, prevention and treatment of cancer. The majority of this funding was allocated to basic research, and the results have been spectacular.

We now know that cancer is caused by mutations and malfunctioning of genes that control cell proliferation and function and genes that guide the repair of damaged DNA. For most cancer cases we know that a number of abnormal genes are involved, and that there are further genetic changes as the cancer progresses.

The good news is that new therapies are being developed aimed at these targets. But the process of cancer drug development remains slow, expensive and inefficient, with inadequate methods for correctly making "go" or "no-go" decisions along the way.

How can we shorten the timeline for new cancer drug development? No single remedy will accomplish this goal, but many, taken together, may succeed.

We need to continue funding research to design better preclinical models for testing new anticancer agents. Information from appropriate animal models must be integrated with discoveries in systems biology that synthesize knowledge about the numerous molecular pathways controlling cell cycle progression, programmed cell death, DNA stability and stem cell differentiation.

We must carry out clinical trials of new agents on patients with early stage disease and take advantage of statistical techniques for moving rapidly from Phase I/II into Phase III protocols. Clinical trials must include mechanistic studies documenting the molecular changes in the patient's cancer cells that result from administration of targeted therapies.

Pharmaceutical companies and the FDA must develop guidelines that enable new targeted agents, which may be active against only a minority of cancer patients, to be used earlier in combinations that target more than a single gene abnormality.

Pharmaceutical companies, the National Cancer Institute and payers such as HMOs and Medicare must invest in research to discover and validate markers that will identify patients who are most likely to respond to a new therapeutic agent. The next step is to accurately predict whether a patient is responding to a particular treatment without having to wait for data on actual prolongation of life. Pharmacogenomic research exploring genetically determined differences in drug metabolism and research in molecular imaging must proceed in parallel.

We need new mechanisms of grant funding and industrial contracts that support large-scale collaboration between laboratory researchers and clinical investigators who may be from multiple institutions as well as industry. Methods to deal with data sharing and the logjam of intellectual property issues should be developed and widely adopted.

There must be other gold standards for academic promotion besides being the primary recipient of a NIH funded grant (R01), in order to offer incentives and reward researchers who participate in collaborative clinical studies.

Academic institutions need to provide outstanding training programs and mentoring for their clinical researchers in tandem with "protected time" for clinical investigation similar to that provided for laboratory researchers. Peer-reviewed journals and promotion and tenure committees should develop ways to identify and reward those who participate in collaborative efforts.

Physicians must agree to collect and record clinical information and research data in a standardized way for easy access to all interested investigators. Electronic medical records could then be mined for correlations of molecular and diagnostic information with outcomes and responses to therapy — so that every patient is potentially a source of research data.

We have to simplify research policies and regulations in order to avoid duplication of review processes. Acceptance of a protocol by a single, lead institution should lead to rapid approval in other institutions.

The federal government and other payers need to support the costs of clinical care that involves experimental therapies, including the off-label (not approved by FDA) use of drugs against new tumor targets when they are being studied in well-designed clinical trials.

Only a small minority of cancer patients enter into clinical trials. Advocates and survivors should be active participants with caregivers, offering patient education and explaining the benefits of participation in clinical trials.

Clinicians and researchers need to emphasize the critical importance of each person in reducing the risk of death from cancer. Many cancers could be avoided if individuals would take greater responsibility and accountability for making use of existing knowledge to alter their lifestyles. Research is needed to improve our ability to promote and facilitate lifestyle change.

My sense is that the NIH and several pharmaceutical companies are beginning to think along these lines. Academia should be leading the efforts.