Cancer Signaling and Microenvironment Program

PROJECT SUMMARY/ABSTRACT – CANCER SIGNALING AND MICROENVIRONMENT PROGRAM The Cancer Signaling and Microenvironment (CSM) Program studies signaling processes, their cancer cell- intrinsic adaptation, and how they are affected by extrinsic cell-cell communication and components of the microenvironment. The holistic perspective that we bring to the study of cancer biology allows for development of new translational strategies to attenuate these signals, and it enables us to better serve patients in our Catchment Area (CA). CSM is a new program resulting from the extensive Fox Chase Cancer Center Strategic Planning that occurred in 2021-2022, which sought to optimize the research portfolio and respond to prior CCSG critiques of the previous program organization. The two overarching aims of the Program are to study “Signaling” (Aim 1) and the “Microenvironment” (Aim 2). Aim 1 focuses on studying proteins at the molecular level, exploring in detail how their activation/inactivation mediates oncogenic signaling. Aim 2 focuses on defining bi- directional signaling between cancer cells and stromal extrinsic factors, including interactions with immune and cancer-associated fibroblastic cells, cytokines, and the extracellular matrix. The CSM Program is explicitly designed to foster collaborative synergies between the Program’s laboratory and clinical researchers. The CSM Program is jointly led by John Karanicolas and Edna Cukierman. Together, they bring highly complementary expertise to support the CSM mission: Karanicolas brings signaling expertise through his cancer chemical biology/drug discovery focus, and Cukierman brings microenvironment expertise through her focus on the interplay of cancer cell-intrinsic and -extrinsic factors. CSM comprises 68 members who are supported by $9.5M (DC) in total peer-reviewed grant funding, of which $3.9M is from NCI. CSM members have contributed to key awards including a U54 grant from NCI’s Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT), and a Stand Up to Cancer (SU2C) grant to promote diversity in clinical trials. During this reporting period, CSM members authored more than 1,000 publications, including 19% intra- programmatic 21% inter-programmatic and 75% inter-institutional collaborations. Impressively, 28% of CSM publications were published in journals with impact factor >10. CSM is a fundamentally interdisciplinary program that integrates faculty with a broad spectrum of complementary expertise. Laboratory investigators work closely with clinical members in a bi-directional manner: community and clinical needs drive laboratory research questions, and discoveries from the laboratory can be rapidly translated to the clinic. Embedding CSM members within the Community Outreach and Engagement efforts also ensures that our Program aligns to these important goals to prioritize research on the cancers that dominate our CA and deemed high priority cancers in the FCCC strategic plan.