Battling the hematological malignancies: The 200 years' war

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Abstract

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. ©AlphaMed Press.

Author-supplied keywords

  • *hematologic malignancy/dt [Drug Therapy]
  • *hematologic malignancy/ep [Epidemiology]
  • *hematologic malignancy/et [Etiology]
  • Hodgkin disease/rt [Radiotherapy]
  • United States
  • acute granulocytic leukemia
  • acute leukemia
  • acute lymphocytic leukemia/dt [Drug Therapy]
  • aging
  • angiogenesis inhibitor/pd [Pharmacology]
  • antimetabolite/pd [Pharmacology]
  • antineoplastic antibiotic/dt [Drug Therapy]
  • antineoplastic antibiotic/pd [Pharmacology]
  • arsenic trioxide
  • azacitidine/pd [Pharmacology]
  • bisphosphonic acid derivative/pd [Pharmacology]
  • bleomycin sulfate
  • bleomycin/dt [Drug Therapy]
  • bleomycin/pd [Pharmacology]
  • bortezomib
  • busulfan/dt [Drug Therapy]
  • busulfan/pd [Pharmacology]
  • cancer growth
  • cancer radiotherapy
  • cancer regression
  • cancer research
  • cancer risk
  • cancer stem cell
  • cancer survival
  • cancer therapy
  • carboplatin/pd [Pharmacology]
  • carmustine
  • cell death
  • cell heterogeneity
  • cell survival
  • chlorambucil
  • chlormethine
  • chronic lymphatic leukemia
  • chronic myeloid leukemia
  • cisplatin
  • cladribine/pd [Pharmacology]
  • clofarabine/pd [Pharmacology]
  • cyclophosphamide
  • cytarabine
  • dacarbazine
  • dacoge
  • dasatinib
  • daunorubicin/dt [Drug Therapy]
  • daunorubicin/pd [Pharmacology]
  • dexamethasone/do [Drug Dose]
  • dexamethasone/pd [Pharmacology]
  • doxorubicin
  • droxia
  • drug cost
  • drug industry
  • drug mechanism
  • drug targeting
  • etopofos
  • etoposide/pd [Pharmacology]
  • fludarabine phosphate
  • gemtuzumab ozogamicin/ae [Adverse Drug Reaction]
  • gemtuzumab ozogamicin/pd [Pharmacology]
  • genetic predisposition
  • genetic variability
  • glucocorticoid/pd [Pharmacology]
  • government
  • growth inhibition
  • histone deacetylase inhibitor/pd [Pharmacology]
  • human
  • hydroxyurea
  • ibritumomab tiuxetan
  • idarubicin
  • ifosfamide
  • imatinib
  • incidence
  • lenalidomide
  • lifespan
  • lomustine
  • long term care
  • lymphoma/dt [Drug Therapy]
  • melphalan
  • mercaptopurine/pd [Pharmacology]
  • methotrexate/pd [Pharmacology]
  • methylprednisolone
  • microorganism
  • mitosis inhibition
  • mitoxantrone
  • monoclonal antibody/ae [Adverse Drug Reaction]
  • myeloma
  • nilotinib
  • nonhodgkin lymphoma
  • oncogene
  • oncoprotein/ec [Endogenous Compound]
  • paclitaxel/do [Drug Dose]
  • paclitaxel/pd [Pharmacology]
  • palliative therapy
  • pamidronic acid/pd [Pharmacology]
  • patient care
  • phenotype
  • phototherapy
  • prednisone/do [Drug Dose]
  • prednisone/pd [Pharmacology]
  • priority journal
  • procarbazine
  • proteasome inhibitor
  • protein tyrosine kinase inhibitor
  • recombinant alpha2a interferon
  • recombinant alpha2b interferon
  • retinoic acid/pd [Pharmacology]
  • review
  • rituximab/ae [Adverse Drug Reaction]
  • rituximab/pd [Pharmacology]
  • tabloid
  • teniposide
  • thalidomide/pd [Pharmacology]
  • thalmid
  • tioguanine
  • topotecan
  • treatment failure
  • treatment outcome
  • unclassified drug
  • unindexed drug
  • unspecified side effect/si [Side Effect]
  • vinblastine sulfate
  • vincristine sulfate
  • vorinostat/pd [Pharmacology]
  • war
  • zoledronic acid XT - unspecified side effect / si

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