Many cancers are glucose-dependent and have a higher rate of glycolysis, as described by the Warburg effect. Reducing the amount of free glucose will starve cancers. Medications that control blood glucose levels, including Metformin, change the intestinal biome by increasing desirable commensal bacteria, causing a drop in A1C. With the drop in glucose, many cancers can modulate metabolism to lipids, so a low-carbohydrate diet will keep the cancer from growing. Cancer can mask the immune system, turning off PD-L1 (Programmed Death Ligandsup-1/sup) and increasing the expression of CD47, the “do not eat me protein. CD47, a protein overexpressed on many cancer cells to prevent macrophages attacks. CD47 does this by binding to Signal Regulatory Protein Alpha (SIRPα) on macrophages. 4-Methylumbelliferone (4-MU) will limit the amount of masked CD47. 4-MU also has other benefits. It will protect the integrity of the B cells but also promotes insulin secretion to help cope with the degradation of B-cell function due to immune destruction. This might offset the side effects of Pembrolizumab (Keytruda), a therapeutic monoclonal antibody which targets and activates PD-1 on immune cells. PD-1 is a molecule that is found on killer T Cells and natural killer cells, which target any cell that does not display the MHC-2 cell surface molecule. These two changes, PD-L1 activation and CD-47 limitation, make cancer visible and vulnerable to Natural Killer cells, Killer T Cells, and macrophages. Pembrolizumab (Keytruda) can have toxic side effects, including a spike in blood sugar, which can damage B Cells, type 1 diabetes, and pancreatitis, though these are considered rare side effects. In Theory, Metformin and 4-MU will inhibit this occurrence with an improvement in gut bacteria and increasing insulin, and therefore lowering the risk to the pancreas and protecting B cells.
John Claras (Mon,) studied this question.