Mechanisms of Cancer Biology Program (MCBP)

Program Co-Leaders: Greg Longmore, MD, Sheila Stewart, PhD and Roberta Faccio, PhD

Overview:

The long-term goal of the Mechanisms of Cancer Biology Program (MCBP) is to identify and map the complex cellular mechanisms that drive cancer development, progression, and metastasis. To accomplish this goal, members of the MCBP are identifying factors (biochemical and physical), signaling pathways and the cellular basis for the communication between tumor and stromal cells that drives tumorigenesis. Together this approach will lay the framework for the design of specific therapeutic modalities. The MCBP is organized around two working groups termed the, (1) Cell Autonomous Cancer Drivers (CACD) and (2) Cancer Cell Nonautonomous Drivers (CCND). Recognizing the importance of the co-morbidities associated not only with the disease but the treatments deployed to fight it, MCBP is developing a third group referred to as Cancer Co-Morbidity Drivers (CCMD). Together these thematic groups include individuals working to discover how cell autonomous mutations and stromal cells, extracellular matrix structural proteins, growth factors, and cytokines interact to modulate tumorigenesis. Further, as cancer therapies become more effective at reducing mortality, cancer survivors are increasingly faced with therapy-induced co-morbidities that can significantly impact their quality of life. Thus, MCBP members also focus on the mechanisms that drive therapy-induced co-morbidities. The MCBP primarily performs basic cancer biology research and discovery, and is structured to interface with other programs within the Siteman Cancer Center (SCC) that are positioned to translate research breakthroughs into patient care, particularly in genetics, molecular and cellular cancer biology, and functional genomics. The MCBP members are currently developing a number of therapeutic drugs that were identified using this approach.

Aims:

The MCBP has three specific aims.

1. Identify the key cell autonomous changes within an incipient tumor cell that initiates tumorigenesis and drives tumor progression. To accomplish this Aim, we have developed a working group referred to as the Cell Autonomous Cancer Drivers (CACD). The MCBP members within this group focus on mutational, epigenetic and metabolomic drivers that arise within incipient cells and contribute to the transformation process, tumor progression, and development of therapy resistance.
2. Identify key communication molecules and pathways that facilitate tumor-stromal interactions to affect tumor cell proliferation, survival, adhesion, motility, and therapy resistance. To accomplish this Aim, a second working group referred to as Cancer Cell Nonautonomous Drivers (CCND) is populated with individuals focused on understanding how the TME communicates with an incipient tumor cell to drive transformation, tumor progression, and therapy resistance. This group takes a broad view of the TME and focuses on cells and the structural (i.e., extracellular matrix) component of the TME.
3. Translate MCBP basic science discoveries to the bedside by fostering intra-programmatic collaborations among MCBP researchers and clinician-scientists and by building an interface to foster inter-programmatic collaborations between MCBP working groups and translational investigators across all SCC research programs. Recognizing the importance of translating basic science findings to the clinic, members of MCBP are identifying putative therapeutic targets. In several instances, these targets are now moving towards clinical trials in collaboration with members of other SCC programs.

Fact and Figures:

• MCBP has 40 members from 12 departments and three schools, and is supported by $15.1 million in funding, with $4.3 million from the NCI and $7.2 million from other peer-reviewed funding sources.
• MCBP members published 711 peer-reviewed papers during 2014–2018, with 142 (20%) papers in journals with impact factors ≥10.
• MCBP members also engaged in extensive collaborative interactions, with 172 (24%) inter- and 108 (15%) intra-programmatic publications.

Recorded program seminars and events are available at this link on WUSTL Box.