Pancreatic Cancer Research: New Tools Will Aid Larger Efforts
Last month brought new hope to the research community in the form of two studies focused on genetically engineered mouse models of pancreatic cancer. Pancreatic ductal adenocarcinoma is among the most lethal human malignancies, with a median survival time of 6 months; only 5 percent of patients achieve five years of survival. This dismal prognosis is thought to be related to the absence of early detection methods. Characterization of early-stage disease has been limited by a lack of appropriate models for research.
In the first study, a team of researchers from the Dana-Farber Cancer Institute reported that they had developed a bioengineered mouse model that contains two "signature mutations" seen in the human form of pancreatic cancer. Just as they do in humans, the mutated genes in the mouse model work together to allow the development of premalignant lesions, which in turn lead to full-blown disease.
In the second study, a research team from the Abramson Cancer Center of the University of Pennsylvania developed a pancreatic cancer mouse model that, again, leads to the development of premalignant lesions in the same fashion as occurs in humans. The research team also found there is a proteomic marker for the presence of the precancerous lesion.
These new mouse models offer hope of more novel discoveries. For example, one of the models with premalignant lesions that have an identifiable proteomic signature shows us that we now may be able to identify early markers in the blood of patients with early pancreatic cancer. The other model allows us to better understand the interaction of genetic mutations that promote the development of malignant lesions, which may help us develop new therapies that can inhibit malignant tumor growth.
In addition to this promising research, NCI has been pursuing more rigorous national efforts to reduce the suffering and death due to pancreatic cancer. Since 1997, NCI has increased funding for pancreatic cancer research more than threefold, from $10.2 million to $33.1 million in 2003.
Of course, ensuring sufficient resources is only part of the challenge. We are also committed to providing strong leadership that is fueled by diverse expertise from across the cancer research community. In response to recommendations from the Pancreatic Cancer Progress Review Group, a panel of prominent scientists and advocates, NCI developed a strategic plan focusing on six key areas: improvements in the health of the pancreatic cancer research field; understanding of tumor biology; risk, prevention, screening, and diagnosis; therapy; communications and health care delivery; and resource priorities.
This strategic plan is guiding NCI's efforts in the discovery, development, and delivery of more effective pancreatic disease interventions. In basic research, for instance, researchers funded by NCI are investigating a relationship among aberrant DNA methylation, abnormal gene transcription, and clinicopathological features of pancreatic cancers.
On the development front, researchers at NCI's Center for Cancer Research are leading a phase I clinical trial to evaluate the effect of a novel class of agents that target the chaperone molecule of many signaling molecules involved in malignancies, including pancreatic cancer.
NCI also supports delivery in the form of advanced clinical trials. For example, NCI's Cancer Therapy Evaluation Program is sponsoring phase II and III trials comparing new and existing therapies. In 2003, the Eastern Cooperative Oncology Group launched a phase III trial to evaluate the synergistic effects of oxaliplatin, a chemotherapeutic agent that is effective in treating metastatic colorectal cancer, when combined with standard gemcitabine therapy. In addition, phase III trials set to launch this year will evaluate new agents, the monoclonal antibodies cetuximab and bevacizumab, in combination with gemcitabine. The trial to evaluate bevacizumab grew out of NCI's continuing collaboration with Genentech, Inc. NCI and Genentech also are working together to develop new phase II trials combining bevacizumab with other targeted drugs for patients with pancreatic cancer.
Other important efforts include the recent formation of the Gastrointestinal Malignancy Faculty. This faculty has recruited multidisciplinary clinicians and is early in the process of developing a clinic for patients with malignant and benign pancreatic tumors. All aspects of treatment, including surgery, chemotherapy, and radiotherapy, will be available. The faculty is in the early stages of its work and I am confident that its members will make valuable advances in the area of pancreatic disease.
One notable feature of all these efforts is the highly focused collaboration of basic and clinical researchers, of scientific, financial, and policy planners, and of intramural and extramural NCI researchers. In addition we have benefited from the valuable input from pancreatic cancer survivor groups. I commend each of them for their hard work and dedication. I look forward to the day when our patients no longer suffer and die from pancreatic cancer.
Andrew C. von Eschenbach, M.D.