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    Oncology Oncology Document Transcript

    • N E W YO R K – P RES B Y T ERI AN Month 2004 Oncology Affiliated with COLUMBIA UNIVERSITY COLLEGE OF PHYSICIANS & SURGEONS and WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY Fall 2005 Researchers Unravel Mystery of Hospital Studies Targeted Therapy Multiple Myeloma Pathogenesis for GI Cancers he Multiple Myeloma Program olumbia and Weill Cornell T at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, one of the leading C researchers at NewYork- Presbyterian Hospital are deep into groundbreaking clinical trials and myeloma programs in the United States, is forging ahead with several clinical and basic science investigations translational studies in the fast-develop- that may yield promising new treat- ing field of targeted cancer therapies ments for patients. that they hope will eventually move The clinical trial program includes from laboratories into life-prolonging an investigation of a unique combina- Myeloma cells: Ongoing investigations at clinical practice. The investigative work tion regimen based on lenalidomide, a NewYork-Presbyterian Hospital include studies of new combination regimens for in targeted gastrointestinal cancer thera- new thalidomide analog that has the treatment of multiple myeloma. pies is illustrative of new pharmacologic already shown promising activity in a approaches that may continue to extend variety of hematologic malignancies. patients’ lives and ultimately transform The lenalidomide study is funded in part by a $7.5 million Specialized Center of “intractable” cancers into treatable Research (SCOR) grant from the Leukemia and Lymphoma Society. chronic diseases. see Myeloma, page 7 “Our program in targeted therapies covers most of the major solid tumors TABLE of and lymphomas and leukemias,” said CME CONTENTS Scott Wadler, MD. An example of the ongoing efforts at Announcement the Hospital is the National Cancer Continuing Medical Cancer Prevention Education course: Ongoing trials strive to define the Institute–funded colon cancer trial involving 2 targeted therapies, bevacizu- “Evolving Strategies in 2 molecular signals that drive tumor formation and growth, and improve care, mab and cetuximab, in combination Prostate Cancer” particularly in underserved populations. with a chemotherapy regimen called September 23-24, 2005, at the Crowne Plaza FOLFOX-6, in previously untreated Hotel Times Square Manhattan, New York, NY Neuro-oncology patients with stage IV or metastatic dis- Researchers at NewYork-Presbyterian ease. Bevacizumab blocks cancer cell growth by homing in on the vascular Sponsored by Columbia University College of Physicians and Surgeons and Weill Medical College of Cornell University and NewYork- 4 Hospital are working with targeted pharmacologic agents, stereotactic radio- Presbyterian Hospital. endothelial growth factor (VEGF) surgery, and stem cell transfer. receptor and choking off the cells’ blood supply, whereas cetuximab prevents For more information, Bridging Science and growth by inhibiting the epidermal please visit: Patient Care growth factor (EGF) receptor on the www.nypcancer.org Riccardo Dalla-Favera, MD, is leading the surface of the cell. To register, please call: 6 development of revolutionary new cancer According to Dr. Wadler, Columbia therapies in his new role as Director of the 1-866-697-7755 Herbert Irving Comprehensive Cancer Center. see GI Cancer, page 5
    • N E W Oncology Y O R K – P R E S B Y T E R I A N Tobacco smoke causes mutations in cells that are proliferating. Activation of EGFR signaling or induction of COX- 2 stimulates cell proliferation, which in turn should increase the mutagenicity of tobacco smoke. The results of this study raise the possibility that inhibitors of either COX-2 or EGFR, or both, Ongoing Trials Seek Preventive may have the potential for preventing or delaying the development of tobacco Measures for At-Risk Groups smoke–induced cancer. “These results strengthen the ration- rogress in defining the molecular EGFR. “COX-2 expression was ale for targeting not only COX-2 but P signals that drive tumor forma- tion and growth has provided the basis for new therapeutic strategies. blocked by using either an inhibitor of EGFR activity or an antibody that prevented amphiregulin from binding also EGFR as approaches for reducing the risk for tobacco-related malignancies of the mouth and throat,” according to Columbia and Weill Cornell researchers to EGFR,” he continued. Dr. Dannenberg. Further experimental at NewYork-Presbyterian Hospital are studies in advance of possible clinical looking at issues ranging from the studies are planned. impact of tobacco smoke exposure on In work being performed by Alfred cyclooxygenase-2 (COX-2) expression I. Neugut, MD, PhD, the Caribbean to cancer risk in Caribbean immigrants immigrant populations in New York in New York. The data are being used “[Our] results strength- are being evaluated in regard to their to improve care and identify risk reduc- risks for different cancers, their atti- tion strategies for often underserved en the rationale for tudes toward cancer, and the health- populations. targeting not only care they receive for cancer, both from COX-2 is a proinflammatory protein a socioeconomic standpoint and from a that has been implicated in a wide vari- COX-2 but also EGFR as biological perspective. Eventually, ety of tumors. Epidemiologic studies approaches for reducing studies will be conducted to compare have associated the use of aspirin and changes in the incidence of specific other nonsteroidal anti-inflammatory the risk for tobacco- cancers among immigrants versus the drugs (NSAIDs) that inhibit COX related malignancies of incidence in their native countries, an enzymes with a significantly reduced important step for isolating envi- risk for cancer, particularly gastroin- the mouth and throat.” ronmental risks. However, the data testinal malignancies. Most recently, collected so far have already generated —Andrew J. Dannenberg, MD Andrew J. Dannenberg, MD, evaluated some important theories about cancer the impact of tobacco smoke exposure risk. on COX-2 expression. In work that “It has long been suspected that the was presented at this year’s meeting of higher incidence of prostate cancer the American Association for Cancer among African-Americans in Research, he reported that COX-2 lev- this country was the result of els were increased by as much as 4 some environmental factor, but times in the oral mucosa of active we are finding that the rates smokers versus people who never among individuals with African smoked. Tracing the mechanism, he blood are also very high in and his co-investigators concluded that immigrants from the West COX-2 levels were increased as a Indies,” said Dr. Neugut. downstream consequence of activation Moreover, there appears to be of epidermal growth factor receptor some correlation between (EGFR) signaling. increased risk and the purity of “In an oral cell line, tobacco smoke African ancestry. For example, clearly activated the EGFR, leading to prostate-specific antigen levels enhanced COX-2 gene expression,” Columbia and Weill Cornell researchers at are higher in individuals from noted Dr. Dannenberg. Activation of NewYork-Presbyterian Hospital are seeking to Tobago, where the average indi- EGFR occurred because tobacco improve care and identify risk-reduction strategies vidual is of nearly 100% African smoke stimulated the production and for underserved populations, such as Caribbean ancestry, than in Trinidad, where, release of amphiregulin, a ligand of immigrants in New York. on average, individuals are more 2 Fall 2005
    • likely to be of mixed European and African NewYork-Presbyterian Oncology ancestry. is a publication of the Cancer Centers of NewYork-Presbyterian Hospital. The Cancer Centers are at the forefront of “It is clear that it is very important to rec- cancer screening and diagnosis, basic science, and clinical research. The Cancer Centers serve over 6,500 new can- ognize that the Caribbean immigrant popula- cer patients each year, who receive state-of-the-art multidisciplinary care. The Cancer Centers include the Herbert tion is very heterogeneous, and this provides Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center and us an opportunity to learn much more about the Weill Cornell Cancer Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, which are respec- environmental versus genetic risks for malig- tively comprised of faculty from the Columbia University College of Physicians and Surgeons and the Weill Medical College of Cornell University. nancy,” Dr. Neugut added. Based on the epidemiologic information gathered so far, some initiatives have already NewYork-Presbyterian Oncology Editorial Board been developed to better reach Caribbean Nasser Altorki, MD Alfred I. Neugut, MD, PhD immigrants at risk for cancer. Screening pro- grams specifically designed for the needs of Director, Division of Thoracic Surgery Co-Director, Cancer Prevention NewYork-Presbyterian/Weill Cornell Acting Chief, Division of Medical Oncology immigrants are being contemplated. Professor, Cardiothoracic Surgery Herbert Irving Comprehensive Cancer Center Effective programs cannot be developed Weill Medical College of Cornell University NewYork-Presbyterian/Columbia generically for immigrants but must address nkaltork@med.cornell.edu Professor of Medicine and Epidemiology the very diverse populations of the Columbia University College of Mitchell C. Benson, MD Physicians and Surgeons and Mailman Caribbean, which are separated by culture Chairman, Department of Urology School of Public Health and language. ain1@columbia.edu Urologist-in-Chief “We have been looking at whether immi- Herbert Irving Comprehensive Cancer Center grants from English-speaking islands, such NewYork-Presbyterian/Columbia Dattatreyudu Nori, MD, FACR as Jamaica and Trinidad, are more likely to George F. Cahill Professor and Chairman of Urology Radiation Oncologist-in-Chief, Department of be screened and effectively treated for cancer Columbia University College of Radiation Oncology than those from non–English-speaking Physicians and Surgeons NewYork-Presbyterian/Weill Cornell mcb2@columbia.edu Professor of Clinical Radiology islands, such as Haiti and the Dominican Weill Medical College of Cornell University Republic,” Dr. Neugut reported. “This infor- Riccardo Dalla-Favera, MD dnori@nyp.org mation is critical for determining how to Director provide care for populations at risk.” Herbert Irving Comprehensive Cancer Center Alexander J. Swistel, MD Importantly, the information generated by NewYork-Presbyterian/Columbia Director, Weill Cornell Breast Center Percy and Joanne Uris Professor of Clinical Medicine NewYork-Presbyterian/Weill Cornell these studies may not only help Caribbean Professor of Genetics and Development Associate Professor of Clinical Surgery immigrants but also generate new insights Professor of Pathology Weill Medical College of Cornell University into differences in environment versus genet- Columbia University College of aswistel@med.cornell.edu ics relevant to all populations. Dr. Neugut Physicians and Surgeons suggested that these studies are an important rd10@columbia.edu Scott Wadler, MD source of epidemiologic data that can gener- Director, Solid Tumor Service Andrew J. Dannenberg, MD NewYork-Presbyterian/Weill Cornell ate advances in the understanding of the Co-Director, Cancer Prevention Richard T. Silver Professor of Medicine, Division of pathophysiology of cancer and steps toward NewYork-Presbyterian/Weill Cornell Hematology and Medical Oncology prevention. Henry R. Erle, MD–Roberts Family Professor Weill Medical College of Cornell University of Medicine Weill Medical College of Cornell University Michael Weiner, MD ajdannen@med.cornell.edu Chief, Pediatric Oncology Andrew J. Dannenberg, MD, is Co-Director, Howard Kaufman, MD Herbert Irving Child and Adolescent Oncology Cancer Prevention at NewYork-Presbyterian Center at Morgan Stanley Children’s Hospital of Vice Chairman, Surgical Oncology NewYork-Presbyterian/Columbia Hospital/Weill Cornell Medical Center, and is Associate Director Henry R. Erle, MD–Roberts Family Professor of Hettinger Professor of Clinical Pediatrics Herbert Irving Comprehensive Cancer Center Columbia University College of Medicine at Weill Medical College of Cornell NewYork-Presbyterian/Columbia Physicians and Surgeons University. E-mail: ajdannen@med.cornell.edu. Associate Professor of Surgery mw216@columbia.edu Columbia University College of Physicians and Surgeons hlk2003@columbia.edu Alfred I. Neugut, MD, PhD, is Co-Director, Cancer Prevention and Acting Chief, Division of David Nanus, MD Medical Oncology, Herbert Irving Co-Division Chief, Hematology/Oncology NewYork-Presbyterian Hospital’s Medical Director, Genitourinary Oncology Program Cancer Prevention Newsletter and Comprehensive Cancer Center at NewYork- Web site offer information for pro- Presbyterian Hospital/Columbia University NewYork-Presbyterian/Weill Cornell Professor of Medicine fessionals on the latest develop- Medical Center, and is Professor of Medicine and ments in the field of cancer pre- Weill Medical College of Cornell University vention and screening. Visit Epidemiology at Columbia University College of dnanus@med.cornell.edu Physicians and Surgeons and Mailman School of www.nypcancerprevention.org. Public Health. E-mail: ain1@columbia.edu. 3
    • N E W Oncology Y O R K – P R E S B Y T E R I A N biochemistry that signals such processes as tumor proliferation and angiogenesis. Innovation is important, but a charac- teristic feature of the neuro-oncology programs at NewYork-Presbyterian is the emphasis on coordinating care to employ innovations where there is a consensus Interdisciplinary Collaboration about an opportunity for an improved outcome. With so many advances being pursued simultaneously, this type of con- Spurs Neuro-oncology Initiatives sensus is essential so that patients may be directed to the optimal choice. Indeed, the success of these innovations depends olumbia and Weill Cornell control of brain tumors, Dr. Rosenfeld on careful patient selection. As a result, C researchers at NewYork- Presbyterian Hospital are driv- ing innovations in multiple fields of predicted that his center may have as many as 2 dozen simultaneous, ongoing clinical trials in the near future. Drug physician teams at the Hospital frequent- ly coordinate patient consultations, help- ing the patient meet individually with neuro-oncology, including targeted phar- tests include those funded by grants each of the physicians participating in macologic agents, stereotactic radio- from the National Institutes of Health as care. The stereotactic radiosurgery pro- surgery, and stem cell transfer, with the well as those funded by private industry. gram, which has been innovative in the goal of implementing these advances Much of the progress has been possible use of a gamma knife for excising brain when they offer a potential advantage because of gains in understanding the metastases, is one example. According to over the existing standard of care. It is already standard that an interdis- ciplinary collaboration begins at the time of diagnosis. Treatment options are discussed, and patients are channeled to “The weekly tumor board includes a full spectrum of a course of therapy on which experts specialists, including oncologists, surgeons, and from several disciplines agree. “The weekly tumor board includes a radiologists. We can no longer work in isolation.” full spectrum of specialists, including oncologists, surgeons, and radiologists,” —Steven S. Rosenfeld, MD, PhD noted Steven S. Rosenfeld, MD, PhD. “We can no longer work in isolation.” One of the most significant innovators worldwide in targeted therapy as it applies to the treatment of brain tumors, Dr. Rosenfeld is optimistic about the potential of several new classes of agents, a large proportion of which are in active trials at NewYork-Presbyterian Hospital. “We are looking at a range of agents that can be used alone or in combina- tion, particularly agents that can block signal transduction important to tumor growth and survival,” he said, adding Photo courtesy of National Cancer Institute. that ongoing work with chloride channel inhibitors derived from scorpion venom (a new class of drugs that block the enzymes within a tumor cell responsible for chromosome transport) and agents targeted at receptors unique to malig- nant gliomas (leaving surrounding tissue unaffected) have been the focus of recent PET scan of a 62-year-old man with a brain tumor. neuro-oncology research at the Hospital. Interdisciplinary collaboration among Columbia and Weill Cornell Because of the rapid progress in iden- researchers at NewYork-Presbyterian Hospital is helping to drive tifying new pharmacologic targets for multiple advances in neuro-oncology. 4 Fall 2005
    • Susan Pannullo, MD, care can be rela- in these young patients. tively seamless as experts not only con- “Neuro-oncology is highly collabora- sult, but also collaborate, in day-to-day “Patients are often seen tive at our center,” said Dr. Rosenfeld. management. As a result of the diversity and depth of “Patients are often seen by a neuro- by a neurosurgeon and expertise at NewYork-Presbyterian surgeon and a radiation oncologist on a a radiation oncologist Hospital, the latest advance is never single visit,” reported Dr. Pannullo, more important than the best outcome. who noted that the stereotactic radio- on a single visit.” James Garvin, MD, PhD, is Chief, Pediatric therapy program is a joint effort of —Susan Pannullo, MD Neuro-Oncology, Herbert Irving Com- both the NewYork-Presbyterian/ prehensive Cancer Center at Morgan Stanley Columbia and NewYork-Presbyterian/ Children’s Hospital of NewYork-Presby- Weill Cornell centers. Although the terian/Columbia Univerity Medical Center, gamma knife is used in the treatment and is Professor of Clinical Pediatrics at of both primary tumors and metastatic the pediatric brain tumor program at Columbia University College of Physicians brain cancer, the treatment of metas- Morgan Stanley Children’s Hospital of and Surgeons. E-mail: jhg1@columbia.edu. tases can often be planned as an outpa- New York-Presbyterian/Columbia, and in Susan Pannullo, MD, is Director, Neuro- tient procedure. This allows patients to 3 successive clinical trials he has pursued Oncology, Department of Neurological receive uninterrupted treatment of the a strategy of intensive chemotherapy with Surgery at NewYork-Presbyterian primary tumor. In appropriate patients, autologous stem cell rescue to limit the Hospital/Weill Cornell Medical Center, and the efficacy of the gamma knife in need for radiation. This approach has also is Assistant Professor of Neurological Surgery excising brain metastases exceeds 95%, been promising in children with tumors at Weill Medical College of Cornell while at the same time the risks and that have recurred following standard University. E-mail: scp2002@med.cornell.edu. complications of open brain surgery or radiation and chemotherapy. Patients less targeted radiotherapy are avoided. with refractory tumors are offered investi- Steven S. Rosenfeld, MD, PhD, is Co- Director, Brain Tumor Center at the New Brain tumors are the second most gational agents through the Phase I York-Presbyterian Hospital/Columbia common type of childhood cancer, after Developmental Therapeutics Consortium University Medical Center, and is John and acute lymphocytic leukemia. Treatment of of the Children’s Oncology Group. Elizabeth Harris Professor of Neurology and infants and young children is especially Future plans include an expanded drug Head, Division of Neuro-Oncology, challenging because of the sensitivity of discovery program for pediatric brain Department of Neurology at Columbia the developing brain to the side effects of tumors and a multidisciplinary late effects University College of Physicians and radiation. James Garvin, MD, PhD, leads clinic devoted to optimizing quality of life Surgeons. E-mail: sr2327@columbia.edu. GI Cancer adding that the median survival of [bevacizumab] has a tendency to make continued from page 1 patients with colon cancer used to be 6 you both bleed and clot.” months when 5-fluorouracil Also under way is a large multicenter and Weill Cornell researchers are “very (5-FU) was the only available treat- trial investigating sorafenib in the treat- hopeful” about the trial, which was ment. “Now the median survival is 22 ment of liver cancer. Sorafenib is a new developed by the New York Phase 2 months,” she continued, “and many agent that targets the pathways that lead Consortium of medical centers. Allyson people live longer.” to cancer cell proliferation. Robert Fine, J. Ocean, MD, noted that FOLFOX in Additional studies are examining the MD, is involved in studies that seek to combination with bevacizumab had use of targeted therapies in cancers of translate laboratory research to clinical already shown a survival advantage in the liver and pancreas. One trial will practice. One potential treatment com- stage IV colon cancer. focus on gemcitabine plus bevacizumab bines arsenic, ascorbic acid, and disulfi- “Our study is taking what is a stan- and either cetuximab or erlotinib in pre- ram. Arsenic and ascorbic acid are already dard and adding another monoclonal viously untreated pancreatic cancer used in treating leukemia patients, accor- antibody”—cetuximab—to see if it pro- patients. Erlotinib is a new oral EGF ding to Dr. Fine. They raise the levels of longs survival, she said. receptor inhibitor approved by the FDA free radicals in cells that are driven by Another study will look at FOLFOX for treating non–small-cell lung cancer. mutations in the ras gene. In all, 95% of plus bevacizumab in stage II and III Another trial is looking at bevacizu- pancreatic cancers fall into this category. colon cancer patients whose tumors have mab as a single agent in liver cancer pa- “Addition of disulfiram, at clinically been resected. “We really wanted to tients. The trial is at an early stage, said achievable concentrations, causes the address a pivotal question: whether the Dr. Siegel, but “we’ve actually seen very free radicals generated by arsenic and benefits associated with bevacizumab as good responses.” One issue is that pa- ascorbic acid to deplete ATP energy lev- first-line therapy for metastatic colorec- tients with a history of bleeding problems els preferentially in pancreatic cancer tal cancer can be translated to the adju- are excluded from the study because, she cells with mutant ras,” noted Dr. Fine. vant setting,” said Abby Siegel, MD, said, “liver cancers are very vascular and see GI Cancer, page 8 5
    • N E W Oncology Y O R K – P R E S B Y T E R I A N Dr. Dalla-Favera has dedicated more than 20 years of his career to investi- gating lymphomas, identifying many novel oncogenes involved in their pathogenesis. A major priority for Dr. Dalla-Favera and colleagues has been the study of the function of bcl-6, a Researcher Hopes To Build Bridge proto-oncogene that codes for a B-cell–expressed transcription factor; in many human lymphomas, the regulatory From Science to Patient Care region of this gene is altered. The researcher’s insights into bcl-6 have been translated into new, experimental thera- iccardo Dalla-Favera, MD, one of pies that are currently undergoing clinical R the world’s leading cancer gene- ticists and lymphoma research- ers, is hoping to take a leading role in evaluation in multiple institutions. Dr. Dalla-Favera and colleagues have also studied the involvement of key translating basic science insights into “It has become very oncogenes in chromosomal transloca- revolutionary new cancer therapies in clear that ‘cancer’ is not tions and deletions associated with lym- his new role as Director of the Herbert phomas. They have discovered that lym- Irving Comprehensive Cancer Center at a single disease. For phomas have a unique mechanism for NewYork-Presbyterian Hospital/Columbia each cancer type, we altering genes, called aberrant somatic University Medical Center. hypermutation. Dr. Dalla-Favera has been at have to know the “This mechanism is generating NewYork-Presbyterian/Columbia for distinct mechanisms of genome-wide genetic damage while the more than 15 years and was a founding lymphoma develops,” Dr. Dalla-Favera member of the Institute for Cancer tumor development, the noted. “We are trying to understand Genetics. He has made pioneering con- different genes that are what combinations of genes are altered in tributions to cancer research, authoring different cases—bringing up, again, the more than 250 publications. altered, and the theme that different tumors will have “It has become very clear that ‘cancer’ complex relationship of different characteristics. Our hope is that is not a single disease,” Dr. Dalla-Favera our findings will lead to very personal- said. “For each cancer type, we have to each tumor type with ized therapeutic approaches based on the know the distinct mechanisms of tumor the other tissues in the genetic makeup of particular tumors.” development, the different genes that Dr. Dalla-Favera has received nation- are altered, and the complex relationship host. Only then will we al recognition for his efforts from the of each tumor type with the other tis- be able to develop new Leukemia and Lymphoma Society of sues in the host. Only then will we be America, which presented him with the able to develop new therapies that will therapies.” Stohlman Scholar Award for Leukemia attack the tumor cells specifically where and Lymphoma Research. He has also they are different from normal cells.” —Riccardo Dalla-Favera, MD received 2 MERIT Awards from the Recently, NewYork-Presbyterian/ National Institutes of Health. As princi- Columbia reinvigorated its commit- pal investigator in a study funded by a ment to cancer research and care with prestigious 5-year, $5 million grant from the opening of the Herbert Irving the Leukemia and Lymphoma Society, Cancer Research Center, an 11,000- Dr. Dalla-Favera will examine mecha- square-foot, 11-story facility dedicated nisms of cancer development and evalu- to laboratory cancer research. The Avon ate experimental lymphoma therapies. Foundation Breast Imaging Center is In addition, he is the principal investi- on the first floor. gator in study supported by a $15.5 mil- “These initiatives will facilitate a new lion National Cancer Institute grant that era of clinical and basic cancer researchers hope will yield new insights research,” Dr. Dalla-Favera said of the into molecular mechanisms in the new facility. “We will have an unprece- pathogenesis of breast cancer. “We will dented opportunity to take basic have to build a full axis from basic research from the laboratory and trans- research to therapeutic development, late that into the clinic.” and 1 important area of emphasis will 6 Fall 2005
    • be breast cancer, thanks also to the sup- in chemistry, physics, and bioinformat- Riccardo Dalla-Favera, MD, is Director, port of the Avon Foundation,” he said. ics—all of which have a tremendous Herbert Irving Comprehensive Cancer An important strength of the Herbert impact on modern cancer research and Center at NewYork-Presbyterian Hospital/ Irving Comprehensive Cancer Center, drug development. In addition, research is Columbia University Medical Center, and according to Dr. Dalla-Favera, is its inte- conducted at the Hospital. “Patients have is Percy and Joanne Uris Professor of gration with Columbia University access not only to promising experimental Clinical Medicine, Professor of Genetics College of Physicians and Surgeons, an treatments that could dramatically change and Development, and Professor of Patho- institution known for the depth of its their life expectancy,” he noted, “but also logy (in the Institute for Cancer Genetics) at research resources, not only in traditional to the best multidisciplinary medical care Columbia University College of Physicians medical and biological sciences but also to improve their quality of life.” and Surgeons. E-mail: rd10@columbia.edu. Myeloma improve patient safety while maintain- regulators in myeloma pathogenesis. continued from page 1 ing the favorable patient outcomes seen “We have found that when patients with BTLD. are stable, there is very little proliferation Through the SCOR initiative, the “We fully anticipate that [lenalido- of myeloma cells, but when they relapse Program takes an aggressive and multi- mide] will achieve an impressive com- or develop aggressive disease, there is a disciplinary approach to multiple myelo- plete remission rate, therefore allowing loss of cell cycle control,” he explained. ma, offering patients transplants, vac- patients to achieve long-term survival,” “We have worked for 5 years to elucidate cines, and drugs, along with participa- said Dr. Niesvizky, adding that the BiRD which molecules are most important in tion in clinical trials of all stages of the investigation is just 1 of several ongoing cell cycle control in myeloma. The next disease. Leading the SCOR initiative is clinical trials in which Myeloma Program step is to develop drugs that will target Selina Chen-Kiang, PhD. investigators are playing a major role. those specific molecules.” “Multiple myeloma is a disease that In particular, investigators look for- Drs. Chen-Kiang, Ely, and Niesvizky has been treated, but not cured, for 150 ward to initiating a trial of second-line collaborate with a full team of expert years, which suggests we must forge treatment for multiple myeloma with scientists and physicians who meet reg- ahead with a new approach,” said Dr. dexamethasone plus the proteasome ularly to share new ideas and communi- Chen-Kiang. “Toward that end, we inhibitor bortezomib along with autolo- cate findings in multiple myeloma. have coupled a very strong basic gous stem cell transplant. The investi- “This is a group of people with a research program with a comprehensive gators are also evaluating a new class of common goal—trying to understand the clinical trial program.” drugs, called histone deacetylase disease better to achieve a cure,” Dr. Recently, the Myeloma Program has inhibitors, in 3 separate protocols. Niesvizky said. “In order to do that, we generated a considerable amount of Together, these protocols cover a wide must translate research from the bench excitement by launching a multiple range of patients. to the bedside, and likewise, from the myeloma treatment study evaluating a “Our goal is to improve treatment bedside to the bench.” combination regimen, known as BiRD, and ultimately to find a cure,” Dr. that includes the antibiotic clarithro- Niesvizky explained. “Toward that end, Selina Chen-Kiang, PhD, is Professor of Pathology and Immunology, Department of mycin, lenalidomide, and dexamethasone. we want to investigate treatments for Pathology and Director, Graduate Program in The BiRD regimen represents an im- patients in every stage of the disease.” Immunology and Microbial Pathogenesis at portant next step in the development of Dr. Niesvizky’s focus on treatment Weill Medical College of Cornell University. new therapeutic regimens for multiple and drug trials is just 1 of 3 comple- E-mail: sckiang@med.cornell.edu. myeloma. While the standard of care, mentary aspects of the Myeloma Pro- dexamethasone alone, achieves a re- gram. Those clinical investigations are Scott Ely, MD, MPH, is Co-Director, Immunopathology Core, Specialized Center sponse rate of only approximately 50%, enhanced by the work of Dr. Chen- of Research for Multiple Myeloma at a combination called BTLD (clarithro- Kiang, who leads the research team. Dr. NewYork-Presbyterian Hospital/Weill mycin, thalidomide, dexamethasone) has Chen-Kiang is a molecular immunolo- Cornell Medical Center, and is Associate yielded a response rate of 93% and com- gist who is currently focused on eluci- Professor of Clinical Pathology and plete remission rate of 13% in recent dating the mechanism of cell cycle con- Laboratory Medicine at Weill Medical clinical studies. trol of myeloma pathogenesis. Likewise, College of Cornell University. Unfortunately, thalidomide is associ- the work of Scott Ely, MD, an expert in E-mail: sae2001@med.cornell.edu. ated with debilitating side effects, while hematopathology, plays another distinct Ruben Niesvizky, MD, is Director of the lenalidomide—1,000 times more potent role in this synergy. Notably, Dr. Ely has Multiple Myeloma Program at NewYork- than the parent drug—avoids many of spearheaded efforts to use histology to Presbyterian Hospital/Weill Cornell Medical those side effects. Ruben Niesvizky, identify cell cycle molecules. Comple- Center, and is Assistant Professor of MD, and colleagues hope that the menting Dr. Chen-Kiang’s molecular Medicine at Weill Medical College of BiRD combination, by replacing approach, Dr. Ely is using immunhisto- Cornell University. thalidomide with lenalidomide, will chemical analysis to identify key cell cycle E-mail: run9001@med.cornell.edu. 7
    • Herbert Irving Comprehensive Cancer GI Cancer Center at NewYork-Presbyterian continued from page 5 Studies are examining the Hospital/Columbia University Medical Center, and is Herbert Irving Associate use of targeted therapies in “This induces a form of cell death only Professor of Medicine at Columbia in the tumor cells.” cancers of the liver and University College of Physicians and Surgeons. E-mail: rlf20@columbia.edu. Dr. Fine’s current translational studies, pancreas. as well as his earlier work with a regi- Allyson J. Ocean, MD, is Assistant Attend- men called GTX (the combination of ing Physician at NewYork-Presbyterian gemcitabine, docetaxel, and capecitabine) Hospital/Weill Cornell Medical Center, and in pancreatic cancer patients, help to therapy in general blocks cell growth or is Assistant Professor of Medicine at Weill illustrate the fact, he said, that “if you causes cell stasis while most chemother- Medical College of Cornell University. use good science [and] translate your apy works only in growing cells,” he said. E-mail: ajo9001@med.cornell.edu. findings from the laboratory to the clin- Everyone agrees that it is an exciting ic, you can significantly improve the cur- time for new cancer treatments. “This is Abby Siegel, MD, is Assistant Attending rent state of the art. GTX, developed in the first time we’ve been able to see pa- Physician at NewYork-Presbyterian Hos- our lab, has high response rates and pro- tients living with cancer rather than dying pital/Columbia University Medical Center, longed survival rates [relative] to the of the disease. We’ve been able to extend and is Assistant Professor of Medicine at standard of care.” One “caveat,” he their lives,” said Dr. Ocean. “The other Columbia University College of Physicians and Surgeons. E-mail: aas54@columbia.edu. added, is that “we have to learn how to amazing thing is that the side effects” of use chemotherapy better and then figure these new therapies are “manageable for Scott Wadler, MD, is Director, Solid Tumor out how to add targeted therapy so that the most part, and people are able to live Service at NewYork-Presbyterian Hospital/ there is no antagonism, because we have their lives with these regimens.” Weill Cornell Medical Center, and is Richard found that some targeted therapies are T. Silver Professor of Medicine, Division of actually antagonistic to chemotherapy in Robert L. Fine, MD, is Director of the Hematology and Medical Oncology at Weill the lab.” The reason is that “targeted Experimental Therapeutics Program, Medical College of Cornell University. SERVICE LINE ADMINISTRATOR: Susan R. Silverman, 627 West 165th Street, New York, NY 10032 212.305.1340 E-mail: sus9005@nyp.org R E S B Y T E R I A N Fall 2005 NONPROFIT ORG. NewYork-Presbyterian Hospital U.S. Postage PAID Oncology 525 East 68th Street Permit No. 1517 New York, NY 10021 San Antonio, TX Important news from the Cancer Centers of NewYork-Presbyterian – P Hospital, at the forefront of cancer O R K prevention and screen- ing, diagnosis, treat- YE W ment, basic science, and clinical research. N