Vitamin D3 Supplementation Modulates C-MYC/VEGF and Improves Chemotherapy Outcomes in Metastatic CRC Patients: Integrated Clinical-Mechanistic Evidence.

Authors

Aya M A Rahman, Nivin A Hassan, Marwa S Hamza, Noha Gaber, Mervat M Omran, Samia A Shouman, Salah M Khallaf

Published in

Asian Pacific journal of cancer prevention : APJCP. Volume 27. Issue 6. Pages 2279-2285. Jun 01, 2026. Epub Jun 01, 2026.

Abstract

Systemic chemotherapy with fluoropyrimidine regimens is the cornerstone of management for unresectable metastatic colorectal cancer (CRC). This study aimed to evaluate the clinical outcomes and potential molecular mechanisms of adding vitamin D3 supplementation to fluoropyrimidine-based chemotherapy in metastatic CRC patients.
This study evaluated the clinical effects of vitamin D3 addition to fluoropyrimidine therapy. Serum vitamin D3 levels and expression of vascular endothelial growth factor (VEGF) and cellular myelocytomatosis (C-Myc) were determined at baseline and after two months of therapy. Clinical endpoints such as overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed.
Patients supplemented with vitamin D3 had a significant rise in the median vitamin D3 levels after two months (8 (6-14) to 13.5 (8-16.3) ng/mL; Δ +5.5 (3-8); Wilcoxon p<0.001), whereas those in the control group, who did not receive supplementation, experienced a decline in median vitamin D3 levels (11 (8-14.3) to 9 (8-16.3) ng/mL; Δ -2 (-4 to +1); Wilcoxon p=0.01). Supplementation was also associated with greater downregulation of VEGF and C-Myc expression (p<0.05). The overall response rate was higher in the vitamin D3 group of patients (63.3% vs. 25.8%; p<0.01), and median PFS was significantly prolonged (9.1 vs. 6.5 months; p=0.028).
Our study suggests that vitamin D3 enhances fluoropyrimidine efficacy in metastatic CRC patients by modulating angiogenesis and proliferation pathways, supporting its potential as a safe, low-cost adjunct to chemotherapy.

PMID:
42345177
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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