Support from the Samuel Waxman Cancer Research Foundation provides important laboratory funding for the study of a cellular factor known as NF-?B, which is involved in controlling the expression of a number of genes. Normally NF-?B functions to regulate key immune and inflammatory mechanisms to block infection and to provide cellular responses for healing mechanisms. However, when NF-?B is activated in cancer it provides signals for cell survival and for tumor cell migration and metastasis. Importantly, NF-?B is activated in many leukemias and lymphomas and in a variety of solid tumors (such as breast cancer, prostate cancer, and pancreatic cancer). Additionally, our studies have demonstrated that standard cancer therapies further activate NF-?B and that this often blunts the effectiveness of the cancer therapy.
The goals in my laboratory are to understand the oncogenic processes controlled by NF-?B and to identify potential targets in the NF-?B pathway for therapeutic intervention. In this regard, in the past year of support by the Waxman Foundation, we have shown that one of the regulatory proteins in the NF-?B pathways (IKK?) controls key growth and survival mechanisms found associated with the majority of cancers. Thus, it is our hypothesis that inhibiting this pathway may have therapeutic application in a wide variety of cancers. We are currently working to obtain an inhibitor of this specific pathway to test in our models for cancers. We are optimistic that inhibition of IKK? may prove to be a new breakthrough in cancer therapy. Additionally, we found that Bcl-3, a member of the NF-?B regulatory pathway, functions to suppress the activation of the tumor suppressor p53. Furthermore, we found that Bcl-3 is expressed in a number of solid tumors, including liver cancer where it is found in over 80% of the tumors. We have also continued our studies on understanding how to block NF-?B activation associated with chemotherapeutic and radiation responses. In this regard, we are testing a variety of new compounds to determine if they work synergistically with chemotherapy or radiation. Clinical trials at UNC are underway based on some of our findings.
In summary, pre-clinical studies support by the Waxman Cancer Foundation are (i) providing insight into the molecular and cellular mechanisms associated with cancer and (ii) offering hope for the discovery of new cancer therapeutics.
return to top
