Understanding the basis of cancer to deliver precision clinical care
The Cancer Biology program explores genetic, molecular and cellular mechanisms underlying cancer initiation, progression, and response and resistance to therapy, providing platforms to translate basic science discoveries to clinical care. The program strives to gain insights into therapeutically-targetable pathways in neoplastic and host-derived cells within complex tumor microenvironments that drive malignancy.
Research is organized in three thematic areas:
- Signal Transduction: Members investigate cellular signaling mechanisms relevant to neoplastic cell proliferation, including integrated functions of growth factors, their receptors, intracellular signaling, and transcriptional regulation to identify therapeutic anti-cancer targets and mechanisms of resistance to current therapeutics.
- Carcinogenesis / Genetic Instability: Members investigate cell-intrinsic and -extrinsic mechanisms that predispose to cancer, including regulation of cell-cycle checkpoint control, DNA damage and repair, genetic and epigenetic alterations, and how these events can be impaired during stem cell development. The goal is to understand these relationships to the development of cancer in order to reveal novel targets for therapy.
- Tumor microenvironment: Members investigate the interactions of neoplastic cells with mesenchymal support cells, immune cells, and vascular cells and how those interactions direct proliferation, survival, tumor evolution, and drug resistance. The goal is to reveal novel properties of the tumor microenvironment that represent tractable targets for cancer therapy.
The program supports research and scientific collaboration in the following ways:
- Development and support of state-of-the-art in vitro, ex vivo and in vivo models
- Recruitment of a multidisciplinary faculty focused on preclinical studies
- Organization of discipline-specific and multidisciplinary symposia, retreats, seminars, journal clubs, and educational workshops
- Development of a cancer biology graduate curriculum
- Support for pilot projects to advance methodologies to stimulate collaborations Development of external non-profit and private sector collaborations that provide access to state-of-the-art technologies, reagents and methodologies and commercialization opportunities.
Recent scientific discoveries in the Cancer Biology program include:
- In the signal transduction theme, investigators have identified a specific phosphorylation that stabilizes MYC and profiled a compound that reverses this phosphorylation event, has anti-tumor activity against tumors that overexpress MYC and is headed toward clinical trials.
- In the carcinogenesis theme, researchers have identified a new, essential DNA locus that is present on mammalian chromosomes, the "inactivation/stability center," which is responsible for proper DNA replication timing and structural stability of each chromosome. When this locus is disrupted it leads directly to genome instability and tumor progression.
- Investigators are also developing interventional strategies to enhance cellular repair of UV-induced damage that are moving toward clinical trials.
- In the tumor microenvironment theme, investigators have identified numerous signaling pathways in tumor infiltrating cells that modulate anti-tumor activity that serve as the basis for five ongoing clinical trials.
- In related studies, investigators have identified a cell-cell fusion between macrophages and tumor cells that imparts metastatic behavior to the fusion hybrids.