Battling the Hematological Malignancies: The 200 Years' War

Oncologist - Tập 13 Số 2 - Trang 126-138 - 2008
Marshall A. Lichtman1
1University of Rochester Medical Center, Rochester, New York, USA

Tóm tắt

Abstract Learning Objectives After completing this course, the reader will be able to: Discuss the advances that led to the current state of management of the hematological malignancies.Describe the remaining major hurdles to curing these diseases in patients who do not respond to current therapy.Identify the strategies needed to reach the goal of cure for most (all) patients. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti–folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients) and drug development costs become more expensive, and the significant negative long-term effects of current therapy on both children and adults. These challenges will be gradually overcome, if we (a) develop new models of cooperation among academia, industry, and government, (b) continue the growth of international participation in cancer research (more keen minds to the task), and (c) convince the governments of the world, including that of the U.S., that an investment in minimizing the effects of cancer is as important as defending against other threats to the welfare and longevity of their citizens.

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Tài liệu tham khảo

Kaplan, 1980, Historical aspects, Hodgkin's Disease, Second Edition, 1

Pillar, 1997, John Hughes Bennett and the Discovery of Leukaemia, Proc R Coll Physicians Edinb, 27, 1

Kyle, 1994, Multiple myeloma: How did it begin?, Mayo Clin Proc, 69, 680, 10.1016/S0025-6196(12)61349-4

Putnam, 1983, From the first to the last of the immunoglobulins. Perspectives and prospects, Clin Physiol Biochem, 1, 63

Lichtman, 2000, Commentary on the use of radiotherapy in the treatment of Hodgkin lymphoma, Hematology: Landmark Papers of the 20th Century, 643, 10.1016/B978-012448510-5/50151-5

Goodman, 1946, Nitrogen mustard therapy: Use of methyl-bis(beta-chlorethyl)amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and other allied and miscellaneous disorders, JAMA, 132, 126, 10.1001/jama.1946.02870380008004

Lichtman, 2000, Commentary on the introduction of alkylating agents in the treatment of hematological malignancies, Hematology: Landmark Papers of the 20th Century, 597, 10.1016/B978-012448510-5/50146-1

Pearson, 1949, ACTH-and cortisone-induced regression of lymphoid tumors in man, Cancer, 2, 943, 10.1002/1097-0142(194911)2:6<943::AID-CNCR2820020602>3.0.CO;2-P

Farber, 1948, Temporary remissions in acute leukemia in children produced by the folic acid antagonist 4-amniopteroyl-glutamic acid (aminopterin), N Engl J Med, 238, 787, 10.1056/NEJM194806032382301

Lichtman, 2000, Commentary on the introduction of antimetabolites in the treatment of hematological malignancies, Hematology: Landmark Papers of the 20th Century, 607, 10.1016/B978-012448510-5/50147-3

Wolff, 1999, Chronicle: First light on the horizon: The dawn of chemotherapy, Med Pediatr Oncol, 33, 405, 10.1002/(SICI)1096-911X(199910)33:4<405::AID-MPO12>3.0.CO;2-X

Zubrod, 1979, Historic milestones in curative chemotherapy, Semin Oncol, 6, 490

Mercer, 1999, The dawn of chemotherapy. The team, Med Pediatr Oncol, 33, 408, 10.1002/(SICI)1096-911X(199910)33:4<408::AID-MPO14>3.0.CO;2-O

Frei, 1958, A comparative study of two regimens of combination chemotherapy in acute leukemia, Blood, 13, 1126, 10.1182/blood.V13.12.1126.1126

Rivera, 1993, Treatment of acute lymphoblastic leukemia. 30 years' experience at St. Jude Children's Research Hospital, N Engl J Med, 329, 1289, 10.1056/NEJM199310283291801

Simon, 2006, Early allogeneic stem cell transplantation for chronic myelogenous leukemia in the imatinib era: A preliminary assessment, Blood Cells Mol Dis, 37, 116, 10.1016/j.bcmd.2006.06.006

Waldmann, 2006, Development of antibodies and chimeric molecules for cancer immunotherapy, Adv Immunol, 90, 83, 10.1016/S0065-2776(06)90003-0

Bishton, 2007, Epigenetic targets in hematological malignancies: Combination therapies with HDACis and demethylating agents, Expert Rev Anticancer Ther, 7, 1439, 10.1586/14737140.7.10.1439

Palucka, 2007, Taming cancer by inducing immunity via dendritic cells, Immunol Rev, 220, 129, 10.1111/j.1600-065X.2007.00575.x

Lichtman, 2007, Cigarette smoking, cytogenetic abnormalities, and acute myelogenous leukemia, Leukemia, 21, 1137, 10.1038/sj.leu.2404698

Natelson, 2007, Benzene-induced acute myeloid leukemia: A clinician's perspective, Am J Hematol, 82, 826, 10.1002/ajh.20934

Smith, 2003, Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: The University of Chicago series, Blood, 102, 43, 10.1182/blood-2002-11-3343

Segel, 2004, Familial (inherited) leukemia, lymphoma, and myeloma: An overview, Blood Cells Mol Dis, 32, 246, 10.1016/j.bcmd.2003.10.005

Yan, 2002, Allelic variation in human gene expression, Science, 297, 1143, 10.1126/science.1072545

Sharp, 2005, Segmental duplications and copy-number variation in the human genome, Am J Hum Genet, 77, 78, 10.1086/431652

Grant, 2007, Recent development in pharmacogenomics: From candidate genes to genome-wide association studies, Expert Rev Mol Diagn, 7, 371, 10.1586/14737159.7.4.371

Lichtman, 2004, The relationship of patient age to the pathobiology of the clonal myeloid diseases, Semin Oncol, 31, 185, 10.1053/j.seminoncol.2003.12.029

Rowley, 2001, Chromosome translocations: Dangerous liaisons revisited, Nat Rev Cancer, 1, 245, 10.1038/35106108

Sandberg, 1990, Historical background, The Chromosomes in Human Cancer and Leukemia, Second Edition, 1

Frei, 1965, Progress and perspectives in the chemotherapy of acute leukemia, Advances in Chemotherapy, 269, 10.1016/B978-1-4831-9930-6.50011-3

Salmon, 1973, Immunoglobulin synthesis and tumor kinetics of multiple myeloma, Semin Hematol, 10, 135

Jordan, 2006, Cancer stem cells, N Engl J Med, 355, 1253, 10.1056/NEJMra061808

Lichtman, 2001, The stem cell in the pathogenesis and treatment of myelogenous leukemia: A perspective, Leukemia, 15, 1489, 10.1038/sj.leu.2402247

Roberts, 1997, Measurement of residual leukemia during remission in childhood acute lymphoblastic leukemia, N Engl J Med, 336, 317, 10.1056/NEJM199701303360501

Greaves, 1997, Silence of the leukemic clone, N Engl J Med, 336, 367, 10.1056/NEJM199701303360510

Lichtman, 2000, Interrupting the inhibition of normal hematopoiesis in myelogenous leukemia: A hypothetical approach to therapy, Stem Cells, 18, 304, 10.1634/stemcells.18-5-304

Pappas, 2008, Applying small RNA molecules to the directed treatment of human diseases: Realizing the potential, Expert Opin Ther Targets, 12, 115, 10.1517/14728222.12.1.115

Eckstein, 2007, The versatility of oligonucleotides as potential therapeutics, Expert Opin Biol Ther, 7, 1021, 10.1517/14712598.7.7.1021

Oeffinger, 2006, Childhood Cancer Survivor Study. Chronic health conditions in adult survivors of childhood cancer, N Engl J Med, 355, 1572, 10.1056/NEJMsa060185

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Oncologist

Tập 13 Số 2

126-138

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