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Systems, Pathways & Targets Program (SPT)

The overall goal of the SPT program is to discover new aspects of cancer biology that can be exploited for the development of novel treatments and diagnostics. SPT membership comprises an interdisciplinary group including cell biologists, immunologists, geneticists, developmental biologists, computational scientists, and clinicians. The program leverages these diverse perspectives to build collaborative teams that tackle long-standing problems using bold and innovative approaches. SPT members address themes that can be represented in a Target/Bull’s Eye framework as shown in the figure at right. Working at different scales, from molecules and cells to tissues and organs, SPT members study the fundamental biology of individual cancer cells as well as the interactions among cells in the tumor environment and metastatic sites. Several SPT members are clinical-scientists with independent research programs, and are well positioned to translate discoveries from bench to bedside. Moreover, SPT leadership actively connects basic scientists with clinicians through the Disease-Oriented Teams and the annual Cancer Center retreat. These interactions are leading towards new clinical trials and also facilitate access to tumor tissue for laboratory research projects.

A unique aspect of SPT is the integration of Systems Biology approaches. UC Irvine has an extensive, well-funded, internationally recognized group of systems biology faculty. These scientists use mathematical and statistical modeling to study behavior and organization of cells and tissues. Through the efforts of SPT co-Leader John Lowengrub and other leaders in the Cancer Center, systems biologists at UC Irvine have focused their attention on cancer-relevant problems. This emerging emphasis has resulted in productive collaborations, both intra- and inter-programmatic, and new extramural funding. In future years we expect that teams studying cancer using systems approaches will identify new molecular and cellular targets for intervention.

The breadth of interests and expertise of SPT members have enabled collaborative teams to focus on specific tumors or tissue types. These include groups studying acute leukemia, skin, breast, prostate and colon cancer. Faculty in these areas meet frequently, along with their group members, to exchange ideas and develop collaborations. By devoting resources to these focused cancer themes, SPT maximizes progress toward the identification of targets. To develop knowledge leading to new treatments and diagnostics, SPT proposes three Specific Aims:

1)    To identify key targets in signaling pathways, developmental pathways, and metabolic programs that are relevant to cancer initiation, progression, and therapeutic resistance. In the past funding period, program members identified key targets in signaling pathways including PI3K/mTOR, FAK, RhoJ/PAK, mutant p53, nutrient dependency and others. SPT continues to support these efforts while nurturing emerging projects including promising combination strategies to overcome cancer cell resistance to chemotherapy and targeted agents.

2)    To develop multi-disciplinary teams to study tumor heterogeneity and microenvironment/cellular interactions. The biology of normal and cancer stem cells is a strong focus in SPT. Similarly, SPT systems biologists have demonstrated outstanding progress in the study of pattern formation, cell lineages, cell division and mutational load in tumors. SPT will expand on this unique portfolio of expertise to grow the number of multi-disciplinary teams that can develop testable models of signaling and tumor cell behavior and identify key processes that modulate the tumor microenvironment.

To diversify multi-disciplinary approaches to develop new therapeutic strategies. The program has made substantial impact through encouraging the formation of interprogrammatic collaborations with CSB to develop small molecule therapeutics for cancer and with OIB to develop tools for research, diagnosis and treatment. SPT will increase the number of these interactions to foster the development of even more lead compounds, tools and approaches. In addition, SPT includes more than a dozen MDs or MD/PhDs that have taken the lead in translating their own projects. SPT will mentor these physician-scientists to partner with basic science faculty to move discoveries into the clinic. Partnerships with pharmaceutical companies and start-ups have had an encouraging start. SPT will work with new Cancer Center leadership to help SPT members ensure that promising agents continue their translational trajectory and advance through preclinical and clinical development
 John Lowengrub, Ph.D.  David Fruman, Ph.D.