An animal study by researchers at the University of Texas MD Anderson Cancer Center provides some insight into why chemotherapy remains mainly ineffective in pancreatic cancer. The results, published in Nature (2015;527:525-530) suggest that suppressing the epithelial-to-mesenchymal transition (EMT) cellular plasticity process in combination with gemcitabine could enhance the drug's effectiveness.
The team, led by Raghu Kalluri, MD, PhD, Professor and Chair of Cancer Biology, found that EMT leads to arrest of cancer cell proliferation, causing impaired sensitivity to chemotherapy, impacting the body's ability to effectively respond to such treatment.
“Gemcitabine works primarily on cancer cells that are dividing or proliferating, and when cancer cells suspend their proliferation—such as when they launch an EMT program—anti-proliferation drugs like gemcitabine do not target them well,” Kalluri explained in a news release.
“We found that the EMT program suppressed drug transporter and concentrative proteins, which inadvertently protected these cancer cells from anti-proliferative drugs such as gemcitabine. 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 a higher incidence of metastasis.
“Collectively, our study offers the opportunity to evaluate the potential of targeting the EMT program to enhance the efficacy of chemotherapy and likely targeted therapies.”
The first author of the study, which was funded by the Cancer Prevention and Research Institute of Texas, is Xiaofeng Zheng, PhD.