Tumor Biology

Program Summary/Abstract The overall goal of the Dan L Duncan Comprehensive Cancer Center's (DLDCCC) Tumor Biology (TB) Program is to uncover new cancer cell-intrinsic and extrinsic factors that drive tumor development, progression metastasis and therapeutic resistance. The TB Program has 50 research and 10 clinical members with over $26 million in total direct funding and more than $6 million from the NCI. During the funding period, Program members published 683 papers, 11% in journals with impact factors >20, demonstrating robust intra-programmatic (24%), inter-programmatic (36%), and inter-institutional (64%) collaborations. The Program is focused on two overarching scientific themes - Cancer Progression and the Microenvironment - that support a systems biology approach to understand tumor biology as a whole and translate discoveries to therapeutic approaches. Several teams of investigators approach these themes using genomics, proteomics and mathematical modeling approaches, as well as drug discovery and understanding signal transduction networks. Extrinsic tumor microenvironment studies focus on immunology, reactive stroma, metabolism, and the microbiome. Our basic research has led to the identification of cross-cutting biological mechanisms in several cancer types, modeling that predicts driver genes, and drug discovery to target progression. Microenvironment studies have led to new vaccine and immunotherapy approaches, paradigm-changing real-time mass spectrometry MasSpec Pen technology to evaluate tumor margins, and identification of new metabolic markers that help identify the biological basis of differences in health care outcomes. Together, these studies have identified several actionable targets, leading to the initiation of clinical trials focused on pancreatic cancer, head and neck cancer, and mesothelioma, in line with the strategic goals of the DLDCCC. In addition, studies have led to translation of multi-omics through generation of comprehensive proteogenomic databases. These contributions have substantially advanced our understanding of cancer, improved data analysis methodologies, and broadened data accessibility for the scientific community. The TB Program has successfully conducted and translated basic research to the bedside and will continue to promote these efforts by working closely with the Translational Working Groups to efficiently bring basic discoveries forward to clinical trials. Promoting communication and interactions is another strength of the TB Program, and we will continue to leverage DLDCCC Shared Resources to support members in achieving program goals.