This is a proposal to use cellular differentiation as a way to modify ALA-mediated photodynamic therapy (PDT) in the treatment of cancer and other hyperproliferative diseases. Differentiation therapy is the principle of converting cells to a more differentiated state in order to enhance the response to specific therapies.
The ultimate goal of this project is to improve the treatment of dysplastic Barrett's esophagus (BE) by optimizing photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). The incidence of esophageal adenocarcinoma is rising faster than any other cancer and BE is the primary risk factor for developing this malignancy. PDT has become a commonly used method for eradication of BE with minimal morbidity.
Photodynamic therapy dosimetry is largely based upon empirical dose escalation trials without much attention paid to the individual variations between patients. This study uses basic laboratory measurements and modeling studies to design and develop fundamentally new dosimetry instrumentation which directly measures the pertinent parameters for optimal PDT treatment outcome.
The overall hypothesis of this project is that subcurative PDT of certain tumor types/sites may increase distant metastasis despite reasonable local control, and thus be detrimental to long-term cure.