Pancreatic Cancer: Introduction

Article Outline

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This edition of Seminars in Oncology brings together the perspectives of investigators from many disciplines working to improve the management of pancreatic cancer. The topics covered range from strategies for prevention and screening, identification of biomarkers for early detection, and emerging treatment regimens for resectable, locally advanced, and metastatic disease.

Pancreatic ductal adenocarcinoma is a very aggressive malignancy that disseminates rapidly. There are no early signs and symptoms thus the disease tends to be diagnosed in late stages, beyond hope for cure. In addition, it is relatively resistant to many forms of therapy. Thus, the 5-year survival rate remains at ≤4%. Recent progress in the use of chemotherapy and selected targeted therapeutics has made a modest improvement in the survival of patients with advanced disease and raises hope that, if strategies for early detection could be successful, the cure rate could be enhanced with appropriate multimodality management.

In their discussions of early detection and strategies for screening, Suresh Chari and Marcia Canto, respectively, both emphasize the need to target and enrich high-risk populations and highlight the need for biomarkers associated with early pancreatic adenocarcinoma. Chari reviews promising developments in the field, including a better understanding in the natural progression of pancreatic adenocarcinoma and the importance of diabetes as a possible early sign of disease. Canto discusses inherited disease and the goal of detection and treatment of early pancreatic neoplasia in high-risk families, as well as the importance of incorporating genetic counseling and informed consent based on individualized recommendations for screening.

Michael Goggins writes about the challenges of identifying diagnostic markers for pancreatic cancer and discusses some of the improvements in technologies such as gene expression profiling, proteomics, high-throughput DNA sequencing strategies, and improved chip technologies. He reviews the current status of analyses of pancreatic juice, serum and tumor tissue.

Michael Ujiki and Mark Talamonti provide a review of surgical management of localized, resectable disease and recognize the benefits of increased referrals to tertiary care centers with expertise in these complex pancreas resections. Careful selection of resection candidates is of utmost importance and is enhanced by well-circumscribed criteria. A more sophisticated understanding of technical adaptations in surgery has also added gains. The importance of margin negative resections is underscored.

Historic and evolving adjuvant treatment approaches are presented by Mary Mulcahy, who describes the potential added benefit of maintenance chemotherapy to chemoradiation and the potential advantages of neoadjuvant therapy.

Suzanne Russo and colleagues provide a review of the current status of therapy for locally advanced disease and the numerous ongoing clinical trials seeking to help define optimal treatment. Promising treatment strategies involving the use of targeted molecular and biologic therapies in combination with conventional chemotherapy and radiation are also reviewed.

The relative merits of current chemoradiation therapies are discussed and data from novel chemoradiation studies are presented by Christopher Crane and coworkers. An outline of appropriate patient selection and improved imaging and supportive technologies also is provided.

Eileen O’Reilly and Ghassan Abou-Alfa review the available cytotoxic regimens and studies for advanced disease. The relative merits of single-agent gemcitabine and combination regimens including some new targeted therapeutics are discussed.

Andrew Ko provides an overview of early, current, and unfolding strategies for use of molecularly targeted therapies. Pancreatic cancer remains uniquely challenging in terms of the difficulty in obtaining sufficient cellular material to enable extensive molecular analyses. However, promising developments in both molecular-based technologies and tissue acquisition techniques have allowed for novel approaches to tackle this problem. Ko describes the development of a patient-tailored approach to managing this disease, which will serve as a basis for future individualized therapy.

It is hoped that the reader will find the information in this issue useful in the management of patients at risk for and with pancreatic ductal adenocarcinoma. Perhaps more importantly, we hope this issue will inspire new research directions designed to improve the outcome for patients with this challenging disease.