Since high serine concentrations were observed in the tumor microenvironment (TME) due to dependency of tumor cells on serine biosynthesis [298], combination of SHMT2 or MTHFD2 inhibitors with other inhibitors of the serine synthesis pathway targeting upstream enzymes such as DHFR, PDGH and NRF2 might lead to more robust anti-cancer activity [292] Additionally, given the fact that serine starvation inhibited tumor growth in mouse models, dietary intervention to restrict serine uptake might be helpful for cancer patients. The gene discussed is DHFR; the disease is cancer.