New approaches are needed to treat pancreatic cancer as chemotherapy drugs such as gemcitabine are not effective for many patients, says a new study. New approaches may include enhancing gemcitabine's ability to stop tumor growth.
The study at The University of Texas MD Anderson Cancer Center conducted in mice suggests that suppressing a cellular plasticity process known as epithelial-to-mesenchymal transition (EMT) in combination with gemcitabine, may boost the drug's effectiveness. Study findings were published in the Nature.
"Diagnosis of pancreatic cancer is associated with poor prognosis despite the availability of current therapies," said Raghu Kalluri, M.D., Ph.D., professor and chair of Cancer Biology, and the study's lead author. "Therefore new treatment strategies are urgently needed."
"Gemcitabine works primarily on cancer cells that are dividing or proliferating," said Kalluri. "When cancer cells suspend their proliferation - such as when they launch an EMT program - then anti-proliferation drugs like gemcitabine do not target them well."
"We found that EMT program suppressed drug transporter and concentrative proteins, which inadvertently protected these cancer cells from anti-proliferative drugs such as gemcitabine," added Kalluri. "The correlation of decreased survival of pancreatic cancer patients with an increased EMT program is likely due to their impaired capacity to respond to chemotherapy, leading to overall poor prognosis and higher incidence of metastasis."
Inhibiting EMT program led to enhanced response of tumors to gemcitabine.
"Collectively, our study offers the opportunity to evaluate the potential of targeting EMT program to enhance efficacy of chemotherapy and likely targeted therapies," said Kalluri.