Tumor Microenvironment

UWCCC Tumor Microenvironment Program Summary Co-Leaders: Pamela Kreeger and Josh Lang PROJECT SUMMARY/ABSTRACT Cancer does not develop in isolation, evolving instead in a complex milieu of reactive stroma and immune cells that constitute the tumor microenvironment. Dynamic interactions between cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM) have been shown to enhance tumor growth, initiate the metastatic cascade, and promote treatment resistance in a variety of cancers. Therapeutic advances have confirmed the incredible potential of targeting the tumor microenvironment but also identified unexpected heterogeneity in response and diverse mechanisms of resistance. Therefore, it is the mission of the Tumor Microenvironment (TM) Program to identify microenvironmental changes that occur during tumorigenesis and analyze how the interactions between the tumor cell and microenvironmental components affect tumor formation, growth, metastasis, and response to therapies. Through these research efforts, members of the TM program are identifying new biomarkers and therapeutic approaches. To accomplish these goals, the TM program fosters collaborations between its 33 members from 14 departments across campus, which include biologists, bioengineers, and clinicians. The TM program is pursuing three Specific Aims, with an emphasis on UWCCC priority targets breast and prostate cancer due to their high prevalence in our catchment: Aim 1: Dissect the role of the extracellular matrix in tumor initiation and metastasis. Aim 2: Analyze multi-cellular interactions within the tumor microenvironment during tumor initiation and metastasis. Aim 3: Interrogate the biological interactions in the tumor microenvironment that mediate treatment response and resistance. TM members were supported by $3.5 million direct costs in NCI funding and $5.1 million direct costs in additional peer-reviewed cancer-related support in the last budget year, and were highly productive with 696 cancer- relevant publications during the course of the last grant cycle. Of these publications, 17% were intra- programmatic collaborations and 32% were inter-programmatic collaborations, increases from the previous cycle. In the year 2021 alone, nearly half of publications were collaborative with other institutions.