Invasion and metastasis--recent advances and future challenges.

Abstract

J Mol Med DOI 10.1007/s00109-015-1269-z MEETING REPORT Invasion and metastasis—recent advances and future challenges Ann F. Chambers & Zena Werb Received: 5 February 2015 / Accepted: 19 February 2015 # Springer-Verlag Berlin Heidelberg 2015 Introduction Most cancer deaths are due to metastasis—the spread of can- cer from its site of origin to distant, vital organs—and the physiological damage caused by tumor growth in those or- gans. While the broad outlines of the process of metastatic spread are known, much of the details of the process remain poorly understood. To continue to improve cancer survival rates, we must face and tackle the problems inherent to meta- static disease. Cancers that are detected early, before they are believed to have spread to other organs, are generally treated with more success than cancers that are metastatic at diagno- sis. However, even cancers that are detected early will recur in some patients, but our ability to predict which individuals will have recurrences is limited. Thus, adjuvant therapy is often given to patients with early-stage disease who are believed as a group to be at risk for recurrence, leading to overtreatment of some patients to benefit a subset of them and possibly failing to treat other patients who will eventually develop recurrent disease. Some recurrences can occur years or even decades after apparently successful primary treatment, and research on tumor dormancy is providing insights into these delayed WILLIAM GUY FORBECK RESEARCH FOUNDATION 2014 Forum on Invasion and Metastasis, November 6–9, 2014, Hilton Head, SC A. F. Chambers (*) London Regional Cancer Program, 790 Commissioners Road East, London, Ontario N6A 4L6, Canada e-mail: ann.chambers@Lhsc.on.ca Z. Werb Department of Anatomy, University of California, Box 0452, HSW 1323, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA e-mail: zena.werb@ucsf.edu recurrences. Progress has been made in the basic biology of tumor invasion and metastasis, and in understanding some of the complexities of cancer cell interactions with host cells in their microenvironment. Great advances have been made for many cancers, in terms of molecular markers/subtypes that are associated with favorable versus poor outcome, as well as prediction of response to a growing list of molecularly targeted agents. However, we also recognize that tumors are not static entities, but instead evolve and change over time, and information from a primary tumor specimen may poorly characterize individual metastases that occur years later. Bioinformatic analyses of tumors and their metastases as well as detection and characterization of disseminating tumor cells in blood or bone marrow, over time, are providing a wealth of data to be interpreted. New models are being developed to address problems in metastasis. The challenge is to learn how to harness this growing body of information to help pa- tients with cancer. Can we prevent metastasis? Can we delay appearance of metastases following primary treatment, either through information inherent to the primary tumor, or through life style or anti-metastatic chemoprevention strategies? Can we learn how to better treat metastases once they have developed? In 1983, 10-year-old William (Billy) Guy Forbeck was diagnosed with neuroblastoma. Unfortunately, he succumbed to the disease at age 11. In 1985, Billy’s parents, George and Jennifer Forbeck, established the William Guy Forbeck Research Foundation (WGFRF) in Billy’s memory. The WGFRF website provides more information: www.wgfrf. org. The mission of the Foundation is Bto promote advances in the field of oncology, particularly pediatric oncology, by shortening the cancer research timetable.^ The Annual Forbeck Forum is a cornerstone of the Foundation and was conceived as a small and intimate Bthink tank^ for open