ABSTRACT ? CELL DEATH AND SURVIVAL NETWORKS PROGRAM The long-term goal of the CDSN program is to unravel the mechanisms and signaling networks in normal and cancer cells that govern their ability to either survive or to undergo various forms of death when stressed (as a consequence of either the inherent requirements of uncontrolled cancer cell growth, or chemotherapy). The CDSN program was created in response to new scientific challenges in the field of cell death and in the emerging area of cancer metabolism. The program includes 17 investigators, including 3 adjuncts, with strong expertise in autophagy and cell death, metabolic signaling, and structural and chemical biology, who work in a highly interactive approach with the ultimate goal of efficient translation of our discoveries into more selective and efficacious therapies. The program consists of three well-defined and highly synergistic themes: (1) Metabolic and Stress Signaling, (2) Autophagy and Cell Death, and (3) Structural and Chemical Biology. These themes are conceptually linked, with metabolic and protein stress in cancer cells closely interconnected to cell survival, cell death, and autophagy. Exploiting these and other signaling pathways through chemical biology is expected to lead to new therapies for cancer. The program has reinforced its cancer focus, as suggested by the previous review, and fosters collaborations among its members through joint lab meetings, monthly program meetings, retreats, and mentoring of junior faculty, postdoctoral fellows, and students. As documented by our current annual direct cancer-related funding of $6.8M, the program has been very productive during this period. Program members currently lead or participate in a total of 42 grants including 24 R01s (15 from NCI), and 4 P01s (3 from NCI), and have authored 314 cancer-relevant papers (between 2009 and 2013), of which 31% were collaborative (16% intra-programmatic and 15% inter-programmatic). Of these, 50 were published in 2013, 22% intra-programmatic and 20% inter-programmatic. A central goal for the program for the next five years is to further enhance interactions among members that allow us to address fundamental questions in the area of cancer metabolism and cell survival. We plan to extend our expertise in these areas by recruiting at least one faculty in cancer metabolism and, in collaboration with TMEM, another faculty with interest in metabolism in the tumor stroma, an emerging field at the interface of metabolism, inflammation, and the tumor microenvironment. Another faculty member will be recruited in the area of autophagy in mouse cancer models. Our ability to translate our findings into innovative therapies will benefit greatly from the presence of program members with outstanding expertise in structural and chemical biology and the rational design of drugs based on structural data, combined with the capabilities of the Conrad Prebys Center for Chemical Genomics in medicinal chemistry and high-throughput screening.