title: Durable response of glioblastoma to adjuvant therapy consisting of temozolomide and a weekly dose of AMD3100 (plerixafor), a CXCR4 inhibitor, together with lapatinib, metformin and niacinamide.
abstract: Glioblastoma multiforme (GBM) is a CNS (central nervous system) malignancy with a low cure rate. Median time to progression after standard treatment is 7 months and median overall survival is 15 months [1]. Post-treatment vasculogenesis promoted by recruitment of bone marrow derived cells (BMDCs, CD11b+ myelomonocytes) is one of main mechanisms of GBM resistance to initial chemoradiotherapy treatment [2]. Local secretion of SDF-1, cognate ligand of BMDCs CXCR4 receptors attracts BMDCs to the post-radiation tumor site.[3]. This SDF-1 hypoxia-dependent effect can be blocked by AMD3100 (plerixafor) [4]. We report a GBM case treated after chemo- radiotherapy with plerixafor and a combination of an mTOR, a Sirt1 and an EGFRvIII inhibitor. After one year temozolomide and the EGFRvIII inhibitor were stopped. Plerixafor, and the MTOR and Sirt-1 inhibitors were continued. He is in clinical and radiologic remission 30 months from the initiation of his adjuvant treatment. To our knowledge, this is the first report of a patient treated for over two years with a CXCR4 inhibitor (plerixafor), as part of his adjuvant treatment. We believe there is sufficient experimental evidence to consider AMD3100 (plerixafor) part of the adjuvant treatment of GBM.
  
  
  CONCLUSIONS
  The adjuvant inhibition of GBM vasculogenesis(a process different from local angiogenesis) by specifically blocking the migration of BMDCs to the primary tumor site with inhibitors of the CXCR4/SDF-1 axis represents a potential novel therapeutic approach to GBM. There is significant pre-clinical evidence and validation for its use as demonstrated in a patient derived tumor xenograft model of GBM. Together with other specific anti-tumoral therapies, the active inhibition of vasculogenesis in the adjuvant treatment of GBM is deserving of further exploration.
authors.affiliation: Division of Oncology at UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Adan
authors.initials: A
authors.lastname: Rios
authors.affiliation: Department of Neurosurgery at UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Sigmund H
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Memorial Hermann Hospital, Texas Medical Center, Houston, TX, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Blanco
authors.affiliation: Department of Pathology and Laboratory Medicine at UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Buryanek
authors.affiliation: Department of Neurosurgery at UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Day
authors.affiliation: Adjunct Faculty, Mathematics & Computer Science at University of St. Thomas-Houston, Houston, TX, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: McGuire
authors.affiliation: Department of Pathology and Laboratory Medicine at UTHealth McGovern Medical School, Houston, TX, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
keywords: biomedical analytics; glioblastoma; morphoproteomics; plerixafor; preventative and targeted therapy