The dark side of granulocyte-colony stimulating factor: a supportive therapy with potential to promote tumour progression

Clin Exp Metastasis. 2018 Apr;35(4):255-267. doi: 10.1007/s10585-018-9917-7. Epub 2018 Jul 2.

Abstract

Granulocyte-colony stimulating factor (G-CSF) is one of several cytokines that can expand and mobilize haematopoietic precursor cells from bone marrow. In particular, G-CSF mobilizes neutrophils when the host is challenged by infection or tissue damage. Severe neutropenia, or febrile neutropenia is a life-threatening event that can be mitigated by administration of G-CSF. Consequently, G-CSF has been used to support patients undergoing chemotherapy who would otherwise require dose reduction due to neutropenia. Over the past 10-15 years it has become increasingly apparent, in preclinical tumour growth and metastasis models, that G-CSF can support tumour progression by mobilization of tumour-associated neutrophils which consequently promote tumour dissemination and metastasis. With the increasing use of G-CSF in the clinic, it is pertinent to ask if there is any evidence of a similar promotion of tumour progression in patients. Here, we have reviewed the preclinical and clinical data on the potential contribution of G-CSF to tumour progression. We conclude that, whilst the evidence for a promotion of metastasis is strong in preclinical models and that limited data indicate that high serum G-CSF levels in patients are associated with poorer prognosis, no studies published so far have revealed evidence of increased tumour progression associated with supportive G-CSF use during chemotherapy in patients. Analysis of G-CSF receptor positive cohorts within supportive trials, as well as studies of the role of G-CSF blockade in appropriate tumours in the absence of chemotherapy could yield clinically translatable findings.

Keywords: G-CSF; Metastasis; Therapy; Tumourigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects*
  • Granulocyte Colony-Stimulating Factor / blood
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / blood
  • Neoplasms / blood supply
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / pathology
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Receptors, Granulocyte Colony-Stimulating Factor / blood

Substances

  • Receptors, Granulocyte Colony-Stimulating Factor
  • Granulocyte Colony-Stimulating Factor