Cancer Stress Biology

PROJECT SUMMARY (ABSTRACT) Cancer cells can overcome stress caused by intense, deregulated replication, and can survive, and even thrive, in the adverse, stressful conditions of the tumor microenvironment. Stress responses are also induced by cytotoxic cancer therapies (e.g., photodynamic, radiation therapy) and the inflammation which arises during anti- tumor immune responses. New research is revealing that systemic stress, mediated by a neuro-immune-tumor axis can contribute significantly to tumor progression may thereby link psychological stress such as anxiety in patients, to molecular signaling pathways and immunosuppression. The Mission of the Cancer Stress Biology (CSB) program is to provide a platform for interactive study of stress at these multiple levels so that we can more completely understand the impact of stress in cancer. The unifying goal of members of the CSB program is to apply knowledge regarding stress to improve cancer treatment and quality of life, and also to better understand how stress can affect different populations, including those resulting in cancer disparities. The program is led by Elizabeth Repasky PhD and Anurag Singh MD, who bring complimentary expertise in basic/translational laboratory research and clinical research and brings together 34 individuals (including 8 new and early-stage investigators) from 13 Departments at Roswell Park. Specific Aims of CSB are: 1) Decipher the impact of tumor cell-intrinsic molecular stress pathways. 2) Identify and characterize stress responses generated within the tumor ecosystem and organism. and 3) Evaluate the role of stress as a modifiable risk factor in cancer patients and develop novel therapies that target stress pathways. The program received a score of Outstanding to Excellent in the 2018 review and since then has significantly increased its high impact publications (26% compared to 10% in 2018), peer-reviewed grant funding ($10.9M compared to $5.3M in 2018) and its accruals to clinical trials (312 vs 53 in 2018) that includes a substantial increase in investigator-initiated interventional trials arising from CSB science. Moreover, we have significantly increased our team science around several overlapping research themes which include replication/epigenetic stress, metabolic and adrenergic stress, radiation, and photo/UV induced stress. CSB faculty are focused on research responsive to COE community-identified needs and priorities with a strong focus on research that examines the basic and translational mechanisms linking the social determinants of health to cancer outcomes, a COE priority area. The CSB Program has benefited from use of all Shared Resources and support from Roswell Park. CSB faculty actively partners with CRTEC, with the objective to train the next generation of scientists in cancer stress biology. With a strong funding and faculty base and sustained collaborations inside/outside our Center, CSB is at the forefront of understanding the role of stress in cancer development and developing novel therapeutics to counteract the effects of stress on cancer disparity and treatment responses.