The Cancer Biology (CB) program focuses on basic scientific discoveries relevant to human malignancies. We determine how a normal cell becomes transformed and develops into a cancer. We use biochemical, cell-based and animal models, as well as patient-derived specimens, to evaluate the genetic and proteomic basis of transformation and to characterize how these events alter signaling and metabolism in cancer stem cells and their progeny, as well as in their surrounding tumor stroma. We investigate the transformation and tumorigenic process to expand our understanding of cancer and to provide new markers and targets that can be used diagnostically or therapeutically.
We focus on three themes:
1. Altered signal transduction pathways in cancer cells
Mutations and epigenetic changes in cancer are ultimately expressed as altered cellular signaling, resulting in changes in cell proliferation, survival, and/or motility/invasion. The CB program excels in the analysis of signaling pathways and establishing oncoproteins as potential therapeutic targets.
2. Tumors and their microenvironment within primary and metastatic tumors
There is increasing evidence that tumor cells recruit and educate surrounding stromal cells, for example, turning immune cells into contributors to metastasis and tumor relapse. We analyze the biomechanical properties of the tumor stroma, the role of stromal communication in cancer cell motility, intravasation and angiogenesis, and the hierarchy of communication mechanisms between tumor and stromal cells. We use stroma-derived ECM cultures, multi-spectra analyses of pathology samples, and intravital multiphoton microscopy integrated with machine-learning classification of imaging data.
3. Therapeutically useful properties of normal and transformed stem cells
Stem cells, when transformed, are believed to play a key role in tumorigenesis and in resistance to anti-cancer agents. Our team examines the link among diet, signal transduction, and epithelial stem cell proliferation, the interplay between cancer stem cells and surrounding stromal cells, and the value of stem cell signaling proteins as therapeutic targets.
The 30 interdepartmental members of the CB program are the core of molecular oncology research at FCCC and are heavily involved in early-stage translational efforts to find new drug targets of neoplastic signaling pathways. We plan strategic recruitments to enhance our efforts in aberrant signaling pathways in cancer cells and in the stroma with the emerging field of cancer metabolomics, with the ultimate goal of translating these insights into clinical practice.