Genomics and proteomics in cancer: Proceedings of the 3^rd Samuel A. Latt conference, Detroit, Michigan

The recent completion of the first raw map of the human genome is a monumental task of unfathomable consequences that represents the first page of the first chapter of the Book of Life. Clearly, the practice of medicine will be altered fundamentally in the new post-genomic era in ways in which we can only speculate. This includes the identification of genes (genomics) that are involved in the appearance, progression, and treatment of cancer, what those specific genes do and how they interact in communication networks (functional genomics), and what roles are played by their protein products (proteomics) in molecular pathways. Practical information and insights are being collected now from raw gene sequences that will impact on cancer research, the clinic, and the life sciences. These include: 1) new understandings of the molecular basis for the pathology of cancer that will lead to differential molecular diagnostics and more practical alternatives to therapy; 2) identification of new validated cancer genes that will be used to predict the susceptibility risk of cancer, accurately diagnose it and personalize the treatment and monitoring of individual patients based on their genotype so that physicians will be able to select optimal drugs and drug dosage and reduce adverse reactions; 3) examination of natural genetic variability between and within populations and its impact on cancer through the application of molecular epidemiology; and 4) utilization of genomic information to accelerate the discovery, development and clinical testing of new, more selective, and tumor type-specific anticancer drugs. Progress in the above areas has been substantial and continues to move at an accelerating pace that is becoming difficult to fully appreciate. For this reason, the International Society for Analytical Cytology (ISAC) and the Josephine Ford Cancer Center, Henry Ford Health System, cosponsored the 3rd Samuel A. Latt/Motown Microarray Meeting, Genomics and Proteomics in Cancer. This meeting was chaired by Alexander Nakeff and was held May 1–4, 2001 at the Holiday Inn Hotel/St. Regis in the Automobile Capital of the World (and Home of the World-famous Motown Sound of the 1960s and 1970s), Detroit, Michigan (“Motown, USA”). It provided an attractive venue for extensive networking among the expert speakers and the over 180 attendees from 8 different countries (including China and Japan). Following welcomes by JFCC's director, Ray Demers, and ISAC's president-elect, Harry Crissman, the first morning's highlights included an in-depth analysis of the potential of different platforms for proteomic analysis using 2-D gels (Mike Pisano, Genomic Solutions), liquid protein mass mapping (David Lubman, University of Michigan), and protein chips (Mike Garner, Ciphergen). Because proteomics remains a relatively new discipline, it was clear at the meeting that no single technology predominates at this point in time but that each brings a unique strength and an inherent weakness to this analysis, which depends very much on the questions posed. This was followed by an exciting talk on how cDNA and tissue microarrays are clinically revolutionizing pathology laboratories through miniaturization and robotics (Ollie Kallioniemi, National Institutes of Health [NIH]) and how new microarray-based approaches also permit the study of protein function (Gavin MacBeath, Harvard). The large data sets generated by these advances have created the burgeoning science of bioinformatics. In the afternoon session, John Weinstein (NIH), Brian Haab (Van Andel), and Mike Kane (Genomic Solutions) demonstrated how new data-mining software can be used to create molecular networks within target cells, which explain how physiologic perturbations, including anticancer drugs, may actually work at the gene and protein level. Betty Woo (Cellomics) took this one step further and showed how bioinformatics coupled to multibead assays can be applied at the physiologic level in living cells using flow-based, fluorescence assays. The second morning's highlights showed the power of microarrays in placing the previous phenotypic classification of solid tumors (sarcomas [Larry Baker, University of Michigan], breast and brain [Oliver Boglar, Ford], lung [Ed Gabrielson, Johns Hopkins University], and the molecular continuum from benign to malignant breast cancer [Maria Worsham, Ford]) on a rational molecular basis that has the potential of ushering in individual patient treatment schedules (Todd Golub, Massachusetts Institute of Technology). Two important points were emphasized, namely, that the correct interpretation of microarray data is fraught with substantial pitfalls in the absence of rigorous controls (Ed Gabrielson) and that custom chips may be replaced eventually by a human genome chip comprising all of the known (approximately 35,000) human genes (Todd Golub). The afternoon's highlights included a fascinating look at how microarrays have revolutionized the pharmacology of high-throughput, target-oriented research (Lukas Amler, BMS), generated molecular signals for ovarian tumors (David Smith, Mayo Foundation), and even have significantly impacted on molecular epidemiology of solid tumors (Ben Rybicki, Ford, and Mark Hughes, Wayne State University). The final day was devoted to various microarray applications to anticancer drug discovery and development. The highlights included a fascinating look at corporate decision-making in terms of future projections of the next generation of anticancer designer-drugs made by the second-leading, anticancer drug-development company in the world (Karol Sikora, Pharmacia) and the major role that the National Cancer Institute (NCI) is playing in linking drug sensitivity of designer drugs to their molecular targets through the NCI COMPARE paradigm (Susan Holbeck). Alexander Nakeff and Balanehru Subramanian (Ford) turned the target-oriented approach around by first using the tumor cell as a target to obtain unique agents with in vivo activity before using cDNA microarrays and 2-D gels as complimentary methods to define molecular target-pathways. This session ended with four excellent presentations highlighting the utility of mRNA profiling in testing anticancer drug efficacy (Gerrit Los, University of California at San Diego) and the practical application of 3-D structural genomics in drug design with the advent of rapid and reproducible methods to produce crystals (Sean Buchanan, Structural Genomix), as well as identification of drug targets by CGH arrays (Joe Gray, University of California at San Francisco) and intermediates by cDNA microarrays (Mike Tainsky, Wayne State University). Of interest to ISAC's membership were discussions that took place throughout the course of the meeting concerning cytometric applications with significant potential impact on future developments in genomics and proteomics that included high-speed cell sorting, single cell deposition, and marker quantitation. These developments provide a rationale for a more efficacious choice of fluorescent probes and readouts, including methodologies for their validation, quantitative cellular approaches to address tumor heterogeneity, and, image analysis approaches to laser microdissected cells from tumor biopsies. It was clear from this meeting that information from arrays eventually must be quantitated at the single tumor-cell level, a role that ISAC can fulfill in a major way. The banquet included the premier unveiling of the Samuel A. Latt plaque (with picture and biography of Sam) by ISAC President Lisa Stiano-Coico. The plaque will be a permanent part of these meetings. It displays shields acknowledging the previous two conferences, the first in Toronto, Canada (1997) and the second in Hamilton Island, Australia (1999). All of the participants were invited to submit papers to Cytometry, although not all accepted the invitation. A short submission time was stipulated to expedite peer review and thus to maintain the timeliness of the information by having it published rapidly in a regular edition of Cytometry. Nevertheless, the selection of submitted papers adequately covers the major topics and captures the flavor of this meeting, in a format similar to the successful The Chipping Forecast, which appeared in a January 1999 supplement to Nature Genetics (1999;21[Suppl]).). The feedback following the meeting has been uniformly positive, from attendees, speakers, and the 37 industrial sponsors, of whom 21 exhibited at the meeting. Numerous comments were received from younger attendees (students, post-doctoral and medical fellows) who appreciated the opportunities to communicate freely with the speakers and to discuss with exhibitors their new advances in a relaxed and mutually enjoyable atmosphere. In summary, the third Samuel A. Latt Motown Microarray Meeting was an outstanding success at both the scientific and social levels. In addition, the meeting was an outstanding financial success, making a substantial profit and confirming, yet again, that venues of this type are a most viable proposition and worthy of future support. The meeting highlights the opportunity for ISAC to enter the genomics-proteomics arena as a player by bringing its core expertise to bear on advances in this important and rapidly expanding area of research and development. The guest editors wish to thank all those individuals and organizations that contributed to the success of this meeting: ISAC Council (in particular, Treasurer Maria Pallavicini, and Secretary Peter Rabinovitch) and the ISAC Scientific Advisory and Communications Committees (especially Carleton Stewart, Chair of SCC, for coordinating and expediting peer review of the submissions in the extended abstract format); the Scientific Advisory Committee (Fred Valeriote, Chuck Grieshaber, David Smith, Mike Tainsky, Mark Hughes, Brian Haab); Jan Visser and Kristle Atkinson from the Cytometry editorial office; Web Master Nigel Carter; the Sherwood Group; the Josephine Ford Cancer Center, Henry Ford Health System (particularly JFCC Director Ray Demers) for financial and logistics support; J. Paul Robinson and Steve Dunlop of Purdue University for their invaluable help and advice on the meeting web site; Carole Anne Nakeff and Loretta Lisow, and members of the Drug Discovery and Development Program (JFCC) for their assistance with registration, the outstanding plenary speakers and numerous attendees, the industrial sponsors and exhibitors (especially our Gold Sponsor, Genomic Solutions, and Shannon Richey, their vice president for Genomics business development) whose generous financial contributions were crucial to the meeting's financial success; and the Hotel St. Regis and its great staff (much appreciated, Chef Rob!).

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