The basic immunology of ASCO
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Biomedical subjects
GA Curt
Publications and source records attributed to GA Curt.
The Impact of Fatigue on Patients with Cancer: Overview of FATIGUE 1 and 2.
Fatigue is a complex, multifactorial disorder with physical, mental, and psychological dimensions that has been associated with diminished quality of life (QOL) in patients with cancer. The prevalence and severity of fatigue, however, has only recently been studied systematically. Two national surveys commissioned by The Fatigue Coalition, a multidisciplinary group of medical practitioners, researchers, and patient advocates, whose mission is to study the importance of fatigue for patients with cancer and their caregivers, have assessed the prevalence, severity, and QOL consequences of fatigue in patients with cancer. The most recent survey, initiated in 1998, sought to confirm and extend observations on the prevalence and impact of fatigue in patients with cancer as part of an initiative to develop guidelines for the differential diagnosis and treatment of fatigue. The FATIGUE 2 study probed the emotional, social, physical, and economic impact of fatigue on patients with cancer and their caregivers. Patient perceptions of the professional response to cancer-related fatigue were also assessed. The key findings of these surveys are reviewed. 2000;5(suppl 2): 9-12
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Investment in Research as a National Priority.
The first time a nation made research a national priority was probably in 15th Century Portugal. While the Spanish built large galleons to ferry gold from the New World to Madrid, the Portuguese built small caravels to return with something more valuable: information. A National Navigational Institute was established in Sagres, where Prince Henry collated the raw data being delivered by the caravels: latitude, longitude, ocean depths, coastal landmarks, and current. Slowly, the caravels moved down the western coast of Africa, overcame the nautical and psychological obstacle of rounding the Horn, and slowly pushed up the Eastern coast. Each new voyage built on the incremental knowledge gleaned from the last and the certain knowledge of the ultimate goal. When Vasco DiGama reached India, the price of pepper in Venice plunged. A new route to the spice trade had been established, a route which did not require the payment of costly tributes at regular intervals along the land route, and a wealthy Empire which would last two centuries was established. The National Institutes of Health represent this nation's commitment to the importance of basic research. In the history of all mankind there has never been a greater, more consistent, and publically funded investment to understand the biology of human disease. Like the caravels, research laboratories and clinical trials have steadily moved forward with incremental progress toward a clearly visualized goal-the prevention and treatment of human disease. In the area of cancer research, we have clearly rounded the horn. The understanding of cancer at a basic level has now brought new targets for cancer treatment into sharper focus. We now understand cancer as a genetic disease. No longer do our therapies target a single cancer feature, uncontrolled growth. Instead, new vaccines like MART-1, gp100, p53 and ras peptides are targeting the cancer cell's ability to evade immune surveillance. Anti-angiogenesis agents like endostatin, Col-3, and angiostatin promise to inhibit the tumor's ability to make new blood vessels and convert cancer to a static, chronic disease. One advantage to these new angiogenesis inhibitors is their action against normal endothelial cells, rather than targeting the cancer itself. For this reason, the genetic plasticity of tumor cells, and their ability to develop drug resistance, is no longer relevant. The Clinton administration has recently announced its intention to add $4.7 billion to cancer research, essentially reaffirming the nation's initial investment of the National Cancer Act. The commitment could not have been better timed. When grants are funded at the 20th percentile, peer review does not work well. And when managed care makes clinical research nearly impossible, we erode the purpose of basic research and undermine the essence of our mission: the prevention and cure of human disease. The Administration's investment will prove to be wise. With the knowledge at hand, and the ability to translate this knowledge into new diagnostic, preventive and treatment approaches, we can begin to realistically vision cancer cures. A new era is at hand.
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10th NCI-EORTC Symposium on New Drugs in Cancer Therapy: Dutch Treat Revisited.
Scientific meetings, like living organisms, tend to evolve over time. For example, the yearly ASCO meeting, which began as a small American academic oncology gathering emphasizing clinical research, has grown into a large, international forum which increasingly emphasizes best standard of care and reimbursement issues [Editor's note: see ASCO review by Chabner, Friedberg in this issue, page 263]. One meeting which has remained true to its initial mission is the NCI-EORTC Symposium on New Drugs in Cancer Therapy which occurs every two years in Amsterdam. Originally organized to help coordinate phase I cancer drug development between the United States and Europe, the meeting fills an important scientific niche. Largely because of the clinical trials standards which have been shared in this forum, phase I data from Europe are now used to launch phase II cancer trials in the United States. Today, the meeting focus-really, the meeting's challenge-remains cancer drug development in Europe and the United States.
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Cancer Drug Development: New Targets for Cancer Treatment.
There is often a considerable lapse of time between the definition of what causes a disease in the laboratory and the development of successful therapy. However, the history of medicine teaches us that the need to understand the scientific basis of disease before the discovery of new treatments is both essential and inevitable. During the middle of the 19th century, the work of the great German pathologist, Rudolf Virchow, defined disease as having an anatomic or histologic basis. In the clinic, this scientific perspective would lead to increasingly effective and, often, increasingly aggressive surgical approaches to disease. Later in the 19th century, Koch's discovery of the tubercle bacillus (a discovery Virchow disbelieved and publication of which he thwarted, since he hypothesized that cancer, not microbes, caused consumption!), would define a microbiological basis for disease. With bacteria defined as a major cause of human suffering, the stage was set for the development of the discovery of effective antibiotics. In the early 20th century, the pioneering work of Banting, Best and others would show that disease can also have an endocrine or metabolic basis. This new body of scientific knowledge would lead not only to the specific discovery of insulin as an effective treatment for diabetes but also to a more general understanding of the role of hormones, vitamins and co-factors in human health and disease. Basic medical research and its successful translation into effective treatments has fundamentally altered the cause of human death. In the developed world, where access to the benefit of this work is available, infectious disease is not the problem it was in the days of Pasteur, Metchnikoff and Ehrlich. As we approach the millennium, science is now teaching us that diseases, particularly cancer, can have a molecular or genetic basis. Can successful application of this new knowledge be far behind? We are already seeing the application of this new knowledge in cancer drug screening and cancer drug development. At the NCI, for example, the old in vivo mouse screen using mouse lymphomas has been shelved; it discovered compounds with some activity in lymphomas, but not the common solid tumors of adulthood. It has been replaced with an initial in vitro screen of some sixty cell lines, representing the common solid tumors-ovary, G.I., lung, breast, CNS, melanoma and others. The idea was to not only discover new drugs with specific anti-tumor activity but also to use the small volumes required for in vitro screening as a medium to screen for new natural product compounds, one of the richest sources of effective chemotherapy. The cell line project had an unexpected dividend. The pattern of sensitivity in the panel predicted the mechanism of action of unknown compounds. An antifolate suppressed cell growth of the different lines like other antifolates, anti-tubulin compounds suppressed like other anti-tubulins, and so on. It now became possible, at a very early stage of cancer drug screening, to select for drugs with unknown-and potentially novel-mechanisms of action. The idea was taken to the next logical step, and that was to characterize the entire panel for important molecular properties of human malignancy: mutations in the tumor suppressor gene p53, expression of important oncogenes like ras or myc, the gp170 gene which confers multiple drug resistance, protein-specific kinases, and others. It now became possible to use the cell line panel as a tool to detect new drugs which targeted a specific genetic property of the tumor cell. Researchers can now ask whether a given drug is likely to inhibit multiple drug resistance or kill cells which over-express specific oncogenes at the earliest phase of drug discovery. In this issue of The Oncologist, Tom Connors celebrates the fiftieth anniversary of cancer chemotherapy. His focus is on the importance of international collaboration in clinical trials and the negative impact of unnecessary bureaucracy and regulation. As a student of Tom's in the 1970s in London, working on hepatoma-specific alkylating agents at Charing Cross Hospital in collaboration with his lab on the other side of town, I can attest to the fact that the regulatory hurdles to cancer drug development just twenty years later have added immeasurably to the effort and cost of cancer drug development. However, I look with optimism to the future of cancer diagnosis, prevention and treatment. It is a future where what we are learning now about the molecular and genetic basis of cancer will find their clinical outlet just as surely as the anatomic, microbial, metabolic and endocrine basis for disease has in the past. This new knowledge will provide new techniques in molecular diagnosis, which will allow us to predict which in situ cancers are destined for malignant behavior, and which can be safely watched without the need for intervention. Individual patient risk for particular cancers will be accurately predictable, so that patients can alter lifestyle habits or begin other prevention strategies. Oncogenes and growth suppressor genes give us new targets to inhibit or replace. Tumor-specific kinases will meet their inhibitors. The oncologist will play a leading role in understanding, applying and interpreting this new information in the clinic-an exciting and challenging future!
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