Pancreatic cancer ranks as 3rd cancer fatality world-wide due to the disease presentation at an advanced stage and early metastatic development. The adenocarcinomas, 95% percent of all pancreatic tumors, are notoriously insensitive to chemo- and radiation therapy, which target processes essential for genome maintenance. Gemcitabine, a nucleoside analog that blocks DNA replication, remains the first line of therapy for patients with advanced pancreatic cancer. Even with treatment, however, most patients will not survive more than one year, because of the molecular mechanisms limiting Gemcitabine cellular uptake and activation, and the overall efficacy, as well as the development of chemo-resistance within the first weeks of treatment. Thus, finding new approaches that would enhance the sensitivity of cancer cells to therapy remains an important strategy in the anti-cancer research and drug development.
Summary of the Invention
Researchers from Fox Chase Cancer Center have discovered a new way to enhance the effect of Gemcitabine inhibition with a combined depletion of the Vitamin D receptor (VDR) or its pathway. The methods relate to a combinatory use of various types VDR antagonists and Gemcitabine. The combined treatment results in a synergistic therapeutic benefit, increased susceptibility of the cancer cells to Gemcitabine and improved chemotherapy outcome. Additionally, the therapeutic strategy may involve inhibiting of a major DNA damageresponse protein to increase the expected anti-cancer effect. This novel combined therapy is predicted to be effective beyond pancreatic cancer, in lung, breast, ovarian tumor cells, lymph node tumor cells, bladder tumor cells, prostate tumor cells, or esophageal tumor cells.
Bhattacharjee V. et al., A synthetic lethal screen identifies the Vitamin D receptor as a novel gemcitabine sensitizer in pancreatic cancer cells. Cell Cycle 2014; 13(24):3839-56.
Patent Status US 9,265,787 issued in 2016
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Inna Khartchenko, MS, MBA
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