title: Pharmacologic therapies for infantile hemangioma: is there a rational basis?
abstract: BACKGROUND
  Infantile hemangioma is the most common tumor of infancy. The majority of cases are managed conservatively, but intervention is necessary in approximately 10 percent of cases because of the threat to life or function or because of tissue distortion or destruction. The mainstay treatment for these problematic proliferating infantile hemangiomas is pharmacologic therapy, mostly discovered serendipitously.
  
  
  METHODS
  This review examines the rational basis of the hitherto empirical pharmacologic therapies for the enigmatic infantile hemangioma, in light of new knowledge regarding its biology, including the critical roles of stem cells and the renin-angiotensin system.
  
  
  RESULTS
  Steroids have remained the first-line therapy for problematic infantile hemangioma for over 40 years despite their known side effects and failure rates. Vincristine has emerged as an alternative to interferon for steroid-resistant cases because of interferon's adverse effects, especially neurotoxicity. β-Blockers are now the preferred first-line therapy for problematic cases. There is increasing evidence that infantile hemangioma is a disorder of aberrant proliferation and differentiation of primitive mesoderm-derived neural crest phenotypic cells. This primitive phenotype that gives rise to a hemogenic endothelium intermediate has the ability to undergo primitive erythropoiesis and terminal mesenchymal differentiation.
  
  
  CONCLUSIONS
  The recent discovery of the crucial role of stem cells and the inferred role of the renin-angiotensin system in the biology of infantile hemangioma underscores the possibility of even more targeted therapies, by using modulators of the renin-angiotensin system, on infantile hemangioma. The observation of the potential role of these traditional antihypertensive agents in stem cell biology may lead to better understanding of developmental biology and tumor stem cell growth.
authors.affiliation: Wellington, New Zealand From the School of Biological Sciences, Victoria University of Wellington; the Center for the Study and Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial, and Burns Unit; the Gillies McIndoe Research Institute; the Department of Pediatrics, Hutt Hospital; and the University of Otago.
authors.forename: Tinte
authors.initials: T
authors.lastname: Itinteang
authors.forename: Aaron H J
authors.initials: AHJ
authors.lastname: Withers
authors.forename: Philip
authors.initials: P
authors.lastname: Leadbitter
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Day
authors.forename: Swee Thong
authors.initials: ST
authors.lastname: Tan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006391:Hemangioma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D005938:Glucocorticoids