Newly-identified Pathways Relating Vitamin D to Carcinogenesis: A Review.

BACKGROUND: The epidemiological relationship between vitamin D levels and cancer has been thoroughly investigated. Published data from large studies appear to corroborate a significant relationship between higher serum vitamin D concentrations and improved survival. Mechanistic reviews on commonly-studied cancers - including breast cancer, colon cancer and melanoma - focus predominantly on data from older studies. In outlining avenues for future research, we believe there is utility in summarizing novel findings introduced to the literature. MATERIALS AND METHODS: In this narrative review, we used MEDLINE, PUBMED and Cochrane databases to identify mechanistic studies published from January 1, 2015 onwards exploring this topic. RESULTS: Twenty-five mechanistic studies were included in this review. It was found that vitamin D plays a critical role in both direct (i.e. tumor gene expression, proliferation, invasiveness, sensitivity to chemotherapy etc.) and indirect (i.e. effects on the tumor microenvironment and immunomodulation) tumor suppression mechanisms. CONCLUSION: These newly-identified pathways warrant further research, with the hopes that we may understand how and when vitamin D supplementation can be integrated into precision medicine therapeutics for cancers of the breast, colon and skin. Cancer care providers should consider recommendations to screen for vitamin D deficiency in this population.

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report.

BACKGROUND: Pembrolizumab, an immune checkpoint inhibitor (ICI), is an IgG4 antibody that blocks interaction between programmed cell death protein 1 and programmed death-ligand 1. Myocarditis, an immune-related adverse event, has been reported in thymic epithelial tumours. Pembrolizumab has also been associated with development/exacerbation of myasthenia gravis (MG). CASE SUMMARY: A 70-year-old woman with metastatic thymic cancer presented to the hospital with shortness of breath, 21 days after initiation of pembrolizumab. She was diagnosed with ICI-related myocarditis and was subsequently intubated due to respiratory failure. A dual-chamber pacemaker was placed due to complete heart block with asystole. Her troponin levels were elevated, an electrocardiogram was suspicious for myocardial infarction, but coronary angiogram revealed normal coronary arteries and endomyocardial biopsy confirmed the presence of myocarditis. Treatment was started with high-dose intravenous methylprednisolone and cardiovascular status improved. However, the patient was unable to be weaned from mechanical ventilation and tested positive for acetylcholine receptor binding/blocking antibodies due to de novo MG. After 50 days of hospitalization, she was discharged home in stable condition. A computed tomography scan was performed 6 weeks after pembrolizumab; results showed significant decrease/resolution of all measurable sites of metastatic disease in the lungs. DISCUSSION: This is the first reported case of a patient developing single-agent pembrolizumab-induced myocarditis concomitant with new-onset MG after treatment for advanced thymic malignancy. Additional studies are needed to explore the association between myocarditis, MG, and ICI therapy.