MTHFD2 and cancer: To date, specific MTHFD2 inhibitors have shown impressive therapeutic efficacy in preclinical models of diverse cancer types, particularly exhibiting promising antitumor activities in lung adenocarcinoma cell lines, either as a single agent or in synergy with pemetrexed [44, 82–84].Considering the disparities in tumor metabolism and the immune microenvironment in distinct histologic subtypes of LUADs, metabolic targets represented by MTHFD2 hold promise for developing their application in histologic subtype-directed combinatorial immunotherapy.