| Program Leader: V. Backman, PhD |
|
Program Co-Leader: G. Woloschak, PhD |
|
|
The Cancer Genes and Molecular Targeting Program of the Robert H. Lurie Comprehensive Cancer Center is a basic research program that evolved from the Cancer Genes and Molecular Targeting Program as synthetic chemistry, structural biology and clinical groups have joined teams to address translational aspects of cancer diagnosis and treatment. In this program, fundamental biology groups, whose focus is on cancer relevant genes and processes discover targets, work with groups that make powerful multifunctional small-molecules and nano-scale agents, and target newly identified tumor susceptibility alleles in metastatic cancer. The resulting new molecular entities are then developed in collaboration with clinical research groups as molecular diagnostics and/or therapeutic agents. This is an interdisciplinary program composed of 28 faculty from 12 departments in 3 schools. Between January 2001 and September 2006 there have been 256 cancer-relevant publications from the current program members. Twenty-Six (10.2%) of these publications represent intra-programmatic collaborations and 84 (32.8%) represent inter-programmatic collaborations. Total current cancer-relevant peer-reviewed funding is $9,148,646 (direct) with $2,706,671 (direct) from NCI, and $6,441,975 (direct) from other peer-reviewed sources. The three programmatic themes include: studies of fundamental mechanisms and molecular pathways that control growth, differentiation and oncogenesis; development of novel diagnostic agents and techniques that facilitate early detection of cancer; and, discovery of new anticancer agents using both novel biological insights and recent advances in Nanotechnology. The fundamental mechanisms that control growth and differentiation involve molecules whose aberrant expression in malignancy provide targets for novel diagnostic probes and therapeutic strategies. Program members have elucidated the key genetic, biochemical and structural characteristics of factors associated with cellular transformation. Innovative high throughput, high sensitivity diagnostic methods have been developed for detection of mutations in cancer-associated genes and imaging of early stage tumors. In addition, promising cytotoxic agents are being investigated including arsenical agents that have proven powerful in leukemia treatments, novel purine analogs (8-CL and 8-NH3 Adenosine), and a variety of new polymer nanoparticle forms of established agents such as doxorubicin. This Program serves as a forum to link basic biological investigation with practical applications from the fields of chemistry, cancer genetics and nanotechnology. Program members are highly interactive and collaborate both int- and inter-programmatically on a broad spectrum of translational projects.
Back to top
Members of the Cancer Genes and Molecular Targeting Program are investigating the key genetic, biochemical and structural characteristics of factors associated with cellular transformation. These molecules include oncogenes, tumor suppressor genes and regulatory enzymes involved in cell growth and differentiation. The aberrant expression of these genes is a hallmark of cancer. Members of the Program are studying the structure and functional characteristics of DNA and RNA, including defining essential components involved in transcriptional regulation (Anderson, Mondragon, Radahakrishnan, Widom); evaluating important signaling molecules and enzymes that produce them (Ouchi, O'Halloran, Rosenzweig); and identifying genetic alterations associated with cancer (Huang, Kaul, Ouchi, Pasche,). Further understanding of these concepts will serve as a springboard for new diagnostic tools as well as strategies for the development of new therapeutic agents.
Back to top
There is a critical need for sensitive, specific, cost effective rapid assays to identify genetic mutations associated with cancer and to characterize and validate sensitive new biomarkers that correlate with staging. Results from this Program over the last five years includes advances in cancer diagnosis in the field of imaging, where both new physical modalities and multifunctional agents are in pre-clinical studies (Backman, Hoffman, Meade, Nuygen, O'Halloran, Stupp). Members of the Cancer Genes and Molecular Targeting Program have made significant technologic advances in development of new types of diagnostic methodologies (Barron, Kaul, Levenson, Scarpulla, Mirkin) and in defined new diagnostic and prognostic markers (Soares, Kaul, Hoffman, Huang, Wang).
Back to top
Several advances in the cancer therapeutics arena have emerged from this sub-group. Many of these discoveries arise from interdisciplinary interactions between experts in the fields of Synthetic Chemistry, Nanotechnology and Physiology. A good balance between clinician scientists and basic scientists is indicative of the strong translational character of this group. Drug discovery projects include the synthesis of novel small molecules (Hoffman, Meade, Silverman), polymer nanoparticles (Nguyen, Scheidt, Stupp), modified liposome systems (Nguyen, O'Halloran), and bioinorganic assemblies of established anticancer drugs (Hoffman, O'Halloran, Rosen, Scheidt, Silverman, Stupp and Woloschak), as well as gene therapy (Dean) and chemopreventative agents (Yang). Several teams have developed novel target-based assays and are screening small molecules for anticancer activity (Huang, Ouchi), while others are working on multifunctional agents that can be monitored in situ and deliver anticancer drug cargo (Meade, Nguyen, O'Halloran, Stupp). One of the strengths of this Program is the connectivity between the understanding of the fundamental mechanisms that control growth and differentiation with innovative diagnostic and therapeutic agents.
Back to top
|
|
