Researchers led by Ludwig Princeton Director Joshua Rabinowitz reported in a February paper in Med that the ketogenic diet—high fat, modest protein and very low carbohydrate—synergizes with chemotherapy to triple survival time compared to chemotherapy alone in rigorous mouse models of pancreatic ductal adenocarcinoma (PDAC). The ketogenic diet mimics fasting by reducing circulating glucose and depressing levels of insulin, a hormone that drives tissues and tumors to consume the sugar. Insulin is an important promoter of cancer growth, especially in pancreatic tumors, while glucose is a critically important fuel for cancer cell proliferation. In multiple experiments over many years, mice engineered to develop PDAC or implanted with tumors that resembled those seen in patients were fed either a normal carbohydrate-rich diet or a ketogenic diet and treated with a standard-of-care combination of chemotherapies—nab-paclitaxel (Abraxane), gemcitabine and cisplatin. The mice receiving the chemotherapy and ketogenic diet had deeper and more durable tumor regressions. While the therapeutic benefit did not require the immune system, only mice with intact immune systems were among the long-term survivors. Josh and his colleagues also conducted an intricate examination of how ketogenic diets affect the metabolism of PDAC tumors and identified mechanisms that might account for the therapeutic effect. An ongoing clinical trial (NCT04631445) is currently testing the strategy in PDAC patients.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).