Southern Research scientists are currently engaged in the following basic research initiatives in cancer:
Anticancer Drug Discovery, William Parker, Ph.D.
Dr. Parker is a member of a research team at Southern Research that designs, synthesizes, and evaluates nucleoside analogs in an effort to create new anticancer compounds. A new drug resulting from these efforts, clofarabine, was approved by the FDA in 2004 for the treatment of childhood acute lymphocytic leukemia. Another agent, 4'-thio-arabinofuranosyl cytosine, is currently being evaluated in clinical trials for antitumor activity.
Gene Therapy of Cancer, William Parker, Ph.D.
Dr. Parker is involved in the development of a gene therapy strategy to treat solid tumors. Specifically, this strategy exploits the substrate differences between human and E. coli purine nucleoside phosphorylase to selectively generate toxic purine analogs in tumor cells. This approach to the treatment of solid tumors has led to the creation of PNP Therapeutics, Inc. An IND was approved by the FDA in March of 2010, and a Phase I clinical trial to evaluate the safety and efficacy of this strategy in head and neck cancer patients was initiated in 2011.
Antiestrogen Resistance in Breast Cancer, Jaideep Thottassery, Ph.D.
A primary focus of Dr. Thottassery's work at Southern Research is to elucidate mechanisms of antiestrogen resistance in breast cancer patients. In the two-thirds of breast cancer patients who have estrogen receptor positive (ER+) disease, estrogen plays a critical role in the growth of tumor cells. Tamoxifen, an ER agonist/antagonist, and aromatase inhibitors are used routinely in treatment in ER+ disease, although progression after an initial response remains a significant problem. ICI 182780 (Faslodex), a pure antiestrogen, inhibits the growth of tamoxifen-resistant lines and has also shown effectiveness in tamoxifen-resistant patients, although there were no complete responses. Dr. Thottassery's research seeks to understand the mechanisms of antiestrogen resistance, which could lead to strategies that might either restore or prolong sensitivity to such therapies.
Molecular Mechanisms of Nucleoside Anticancer Agents, Jaideep Thottassery, Ph.D.
Dr. Thottassery is a member of a research team at Southern Research that investigates newer nucleosides and the mechanisms by which their effects are elicited in tumor cells. Southern Research has maintained a nucleoside drug discovery program for several years, and two FDA-approved drugs - Fludarabine and Clofarabine - have resulted from these efforts. Clofarabine was approved by the FDA in 2004 for the treatment of childhood acute lymphocytic leukemia. Another agent, 4'-thio-arabinofuranosyl cytosine, is currently being evaluated for antitumor activity in clinical trials. Southern Research investigates the role of cellular pathways in the effects mediated by these agents.
The DNA Damage Response and Cancer Drug Discovery, Bo Xu, M.D., Ph.D.
Dr. Xu’s research team focuses on studying mechanisms that control the cellular response to DNA damaging agents. These regulatory events are central to two of the major issues in the field of cancer biology: 1) how and when cancers start and progress; and 2) what determines the sensitivity of tumors to therapeutic interventions. Several projects are currently ongoing in the laboratory with fundamental mechanisms on cancer biology as well as novel approaches to anticancer drug discovery.
The Tumor Microenvironment and Drug Sensitivity, Lidija Klampfer, Ph.D.
The microenvironment of solid tumors is characterized by the presence of activated stromal cells, which produce an abundance of inflammatory mediators that have been shown to play a critical role in tumor progression. Macrophages and myofibroblasts are two major components of the tumor microenvironment. Dr. Klampfer and her colleagues are investigating how inflammatory factors produced by macrophages and myofibroblasts modulate oncogenic signaling pathways in tumor cells, including NFκB, Wnt, and STAT pathways. An objective of the research is to understand the nature of tumor-derived factors that are responsible for activation of stromal cells and determine how the presence of genetic alterations in tumor cells alters communication of tumor cells with the stroma. In addition to their effect on tumor growth, factors from the tumor microenvironment are also important regulators of responsiveness of cancer cells to antineoplastic therapies. Dr. Klampfer and her colleagues are testing the hypothesis that proinflammatory factors promote the cancer stem cell phenotype, thereby promoting chemoresistance of cancer cells. It is believed that establishing an understanding of the crosstalk between tumor cells and the tumor microenvironment will reveal novel drug targets for cancer treatment.
Wnt Signaling in Cancer, Yonghe Li, Ph.D.
The canonical Wnt signaling pathway is important in stem cell biology and embryonic development and can lead to tumor formation when aberrantly activated. Dr. Li's research interests center around the canonical Wnt signaling pathway in cancer. Current projects in this area include:
For more information about our capabilities, contact us at: