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

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

doi:10.31557/APJCP.2026.27.6.2279

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

Document Type : Research Articles

Authors

¹ Cancer Biology Department, (Pharmacology and Experimental Oncology), South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

² Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, Egypt.

³ Oncological Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

⁴ Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

⁵ Medical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

10.31557/APJCP.2026.27.6.2279

Abstract

Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

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