Ashok Saluja, Ph.D.
Professor of Surgery
Description of Research
Dr. Saluja’s research is primarily focused cancer therapy and how it can be taken from bench to bedside. Over last 35 years he has been studying the biology of pancreatic diseases. Among these, the most devastating one is the pancreatic adenocarcinoma. Pancreatic cancer is an extremely aggressive disease with a poor prognosis and is the third leading cause of cancer-related death in the US. Every year, more than 50,000 Americans succumb to this disease. Dr. Saluja’s laboratory is interested in the role played by heat shock proteins in the pathophysiology of this resistance. They have demonstrated previously that HSP70 is overexpressed in pancreatic cancer cells and that its inhibition leads to apoptotic cell death. His group has been successful in developing a small molecule inhibitor of HSP70, which they named MINNELIDE. This compound is very efficacious in several models of pancreatic cancer. Minnelide is currently under Phase I clinical trials against gastrointestinal cancers. Dr. Saluja’s group is actively working on the mechanism by which this drug induces tumor regression and pancreatic cancer cell death. Dr. Saluja’s group is also evaluating various naturally-occurring compounds as potential therapies for this deadly disease. They are heavily invested in the studies to elucidate the mechanisms by which Minnelide inhibits HSP70. Their results thus far suggest that triptolide/Minnelide inhibit Sp1, resulting in inhibition of NFkB and subsequently decrease the activity of HSF-1 and HSP70. In addition to pancreatic cancer, Dr. Saluja’s group is testing the efficacy of Minnelide in a number of other cancers. These include Acute Myeloid Leukemia (AML), castration resistant prostate cancer, gastric cancer and melanoma. Since monotherapy is not preferred as a treatment option in any cancer treatment regime, they are also evaluating Minnelide in combination with a number of approved standards of care like Gemcitabine and Abraxane.
- In studies published in Cancer Research, Dr. Saluja’s group demonstrated that HSP70 is overexpressed in pancreatic cancer cells and that its inhibition leads to apoptotic cell death. Inhibiting HSP70 expression is also very effective at reducing the growth of pancreatic tumors in orthotopic models of pancreatic cancer, where it markedly reduced loco-regional spread.
- In collaboration with the Department of Medicinal Chemistry and Center for Translational Medicine at the University of Minnesota, Dr. Saluja’s group successfully developed a small molecule which they named MINNELIDE.
- Dr. Saluja’s lab demonstrated that HSP70 inhibits apoptosis by two independent yet simultaneous means: by attenuating intracellular calcium and by stabilizing the lysosomes.
- Recent findings from Dr. Saluja’s group suggest that HSP70 is protective in pancreatitis and that its upregulation should be beneficial against pancreatitis.
Selected Cancer-Related Publications
Leader of the Multidisciplinary Research Program: Tumor Biology Program