From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM.
Study Goal
The researchers aimed to evaluate the potential antitumor synergism of Vitamin A derivatives (specifically All-Trans Retinoic Acid, ATRA) with Vitamin D and temozolomide in managing high-grade glial tumors.
Results Summary
The study found that Vitamin A derivatives (ATRA) showed antitumor synergism with Vitamin D and temozolomide, potentially improving outcomes in glioblastoma multiforme (GBM). However, excess Vitamin A may contribute to intracranial hypertension, necessitating caution.
Population
Elderly men with glioblastoma multiforme (GBM) and general GBM patients.
Effective Dosage
Not specified
Duration
Not specified
Interactions
Synergistic interaction with Vitamin D and temozolomide; potential intracranial hypertension risk when combined with Vitamin D excess.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
winter birth | increase | GBM | - | - | is associated with higher risk | #1 |
GBM debulking in the winter | increase | mortality | - | - | enhanced mortality | #2 |
higher prediagnosis levels of calcidiol | decrease | GBM | elderly men | - | are associated with lower risk | #3 |
Supplemental Vitamin D | decrease | mortality | GBM patients | - | reduced mortality | #4 |
Expression of Vitamin D Receptor | increase | prognosis | GBM | - | is associated with a good prognosis | #5 |
Vitamin D | increase | neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF | - | - | increases glial tumor synthesis | #6 |
temozolomide and Vitamin D | decrease | tumor | - | - | Antitumor synergisms | #7 |
Vitamin D with Vitamin A derivatives | decrease | tumor | - | - | Antitumor synergisms | #8 |
Vitamin D excess | increase | intracranial hypertension | - | - | may cause | #9 |
Vitamin A excess | increase | intracranial hypertension | - | - | may cause | #10 |
acetazolomide | decrease | pseudotumor cerebri | - | - | may reduce the risk | #11 |
acetazolomide | increase | anticancer activity | - | - | exhibits | #12 |
Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide - CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity.