In the 1920s, Otto Warburg identified the first molecular feature of cancer: altered metabolism in the form of increased fermentation of glucose to lactate. This glucose-avidity of cancer underlies its modern diagnosis using FDG-PET imaging. Subsequent research identified enhanced nucleotide synthesis as another defining feature of cancer, leading to the development of the first class of targeted chemotherapeutics, antifolates. One of these, pemetrexed, discovered at Princeton by late Professor Edward Taylor, remains a first line therapy for lung cancer.
Building on the successes, the Ludwig Princeton Branch will investigate the fundamentals of metabolism, and how these go awry in cancer. Building on the strength of Princeton in the physical sciences and computation, we will innovate new methods for measuring and manipulating metabolism. We will explore the role of metabolism in cancer initiation, with obesity a major risk factor for endometrial, esophageal, liver, kidney, and pancreatic cancer. We will measure metabolic activity during tumorigenesis, from pre-malignant lesions to metastasis, in both tumors and their hosts, and between different cell types in the tumor microenvironment. The resulting knowledge will be used to develop new treatment regimens that manipulate metabolism to suppress tumor growth and augment antitumor immune response.