TAMPA, Fla. – Prostate cancer is the second leading cause of cancer-related mortality in men, resulting in an estimated 27,540 deaths in 2015. Many of these deaths are due to acquired resistance to existing drug therapies. Scientists have been trying to uncover the mechanisms leading to drug resistance to develop better therapies. As a result, Moffitt Cancer Center researchers discovered a novel pathway that cancer cells use to become drug resistant.
Many studies have previously found that a protein called clusterin is highly expressed in a number of different tumors, including prostate, breast, pancreatic, bladder, melanoma and lymphoma. Clusterin expression aids in the development of resistance to cancer chemotherapeutic drugs by blocking cell death. However, it was unknown what cellular pathway causes cancer cells to express high levels of clusterin.
Moffitt scientists discovered that clusterin becomes upregulated in cancer cells due to cross-communication between dying and living cells. Treatment of prostate cancer cells with a chemotherapeutic agent called docetaxel caused dying cells to release a protein called HMGB1. HMGB1 acts as a danger signal and communicated to the neighboring live cells to upregulate clusterin levels, protecting them from the drug cell death.
“These cells can then divide and grow in the presence of the chemotherapeutic agent and become a resistant cell population. This may be one mechanism for the development of chemoresistance in cancer patients,” explained Julie Y. Djeu, Ph.D., scientific director of the Flow Cytometry Core Facility and associate center director of education and training at Moffitt.
The researchers reported that many different chemotherapeutic drugs currently being used in treatment can cause release of HMGB1. These observations suggest that the HMGB1-clusterin communication pathway may contribute to drug resistance to a wide-range of anticancer agents and may be a potential target for novel drugs.
About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 45 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, its contributions to clinical trials, prevention and cancer control. Moffitt is the top-ranked cancer hospital in Florida and has been listed in U.S. News & World Report as one of the “Best Hospitals” for cancer care since 1999. With more than 4,600 team members, Moffitt has an economic impact in the state of $1.9 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, Twitter and YouTube.