Table 1.
Cancer drugs and their mechanism causing hyperglycemia.
| Anticancer Drugs | Mechanism of Action |
|---|---|
| Targeted Agents | |
| IGF-1R inhibitor IGF-1R-specific monoclonal antibodies (dalotuzumab) Small-molecule inhibitors of IGF-1R and IR (linsitinib) Other inhibitors of IGF-1R (ganetespib, ceritinib) |
Inhibit IGF-1R, which is partially homologous to the IR, and block the activation of the Ras/MAPK/ERK and PI3K/AKT/mTOR pathways and thereby block cancer cell growth and proliferation |
| PI3K/mTOR inhibition mTOR inhibitors (everolimus, temsirolimus) PI3K3CA inhibitor (alpelisib) AKT inhibitors (ipatasertib, capivasertib) |
Inhibit the PI3K/Akt/mTOR pathway and thus interfere with malignant cell growth, but may lead to hyperglycemia by interrupting the intracellular response to insulin, causing decreased glucose transport, decreased glycogen synthesis, and increased glycolysis |
| BCR-ABL inhibitors (nilotinib, dasatinib, and ponatinib) | Multi-targeted TKIs that inhibit BCR-ABL and other TKIs such as KIT, PDGFR, DDR, and CSF-1R |
| Anti-EFGR (rociletinib) | Block EGFR pathway and affect downstream signaling cascades, namely the RAS/MAPK/ERK, PI3K/Akt, and JAK/STAT pathways |
| Immunotherapy | |
| Anti CTLA-4 (ipilimumab) Immune checkpoint inhibitors (nivolumab, pembrolizumab) |
Activate T cells and enhance the immune response against malignant cells; treatment could cause autoimmune phenomena including autoimmune diabetes mellitus |
| Hormone Therapy | |
| Somatostatin analogues (octreotide and lanreotide) | Bind predominantly to the somatostatin receptors and suppress insulin secretion |
| Anti-estrogen therapy (tamoxifen, aromatase inhibitors) | Decrease insulin secretion via inhibition of antiapoptotic effects of estradiol on pancreatic β-cells and increase insulin resistance via elevated triglyceride levels and fatty liver |
| Anti-androgen therapy (bicalutamide) | Increase insulin resistance by modulating androgen and androgen receptor signaling pathways in the liver and adipose tissue |
| Miscellaneous | |
| Asparaginase | Hydrolyzes serum asparagine to nonfunctional aspartic acid and ammonia, depriving tumor cells of asparagine |
| Diazoxide | Nondiuretic benzothiadiazine that inhibits insulin secretion |
BCR-ABL, breakpoint cluster region gene–Abelson proto-oncogene; CTLA, cytotoxic T lymphocyte-associated antigen; EGFR, epidermal growth factor receptor; ERK, extracellular signal-related kinase; IGF-1R, insulin-like growth factor type 1 receptor IR, insulin receptor; MAPK, mitogen-activated protein kinase; PI3K/mTOR, phosphatidylinositol 3-kinase/mechanistic target of rapamycin; TKI, tyrosine kinase inhibitor.