A study at The University of Texas MD Anderson Cancer Center may explain why chemotherapy drugs such as gemcitabine are not effective for many patients with pancreatic cancer and perhaps point to new approaches to treatment, including enhancing gemcitabine's ability to stop tumor growth.
The MD Anderson study in mice suggested that suppressing a cellular plasticity process known as epithelial-to-mesenchymal transition, in combination with gemcitabine, may boost the drug's effectiveness. These study findings were published by Zheng et al in Nature.
“Diagnosis of pancreatic cancer is associated with poor prognosis despite the availability of current therapies,” said Raghu Kalluri, MD, PhD, Professor and Chair of Cancer Biology at MD Anderson. “Therefore, new treatment strategies are urgently needed.”
Study Details
Dr. Kalluri's team looked at epithelial-to-mesenchymal transition, an embryonic cellular plasticity program that is hijacked by cancer cells and is thought to help cancer cells migrate to other organs. When cancer cells adopt an epithelial-to-mesenchymal transition program to promote their migration, they generally stop dividing. The research findings indicate that epithelial-to-mesenchymal transition 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,” said Dr. Kalluri. "When cancer cells suspend their proliferation—such as when they launch an epithelial-to-mesenchymal transition program—then antiproliferation 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 antiproliferative drugs such as gemcitabine,” added Dr. 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 the epithelial-to-mesenchymal transition program led to an 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 Dr. Kalluri.
The study was funded by the Cancer Prevention and Research Institute of Texas.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®
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