Why some drugs don’t work against pancreatic cancer

An MD Anderson study may explain why chemotherapy drugs such as gemcitabine are ineffective against pancreatic cancer in some patients. The study also offers suggestions about how to enhance the drug’s ability to stop tumor growth.

Lead study author Raghu Kalluri, M.D., Ph.D., and his team looked at mice to study EMT, an embryonic cellular plasticity program that is hijacked by cancer cells and is thought to help cancer cells migrate to other organs. Cancer cells spread disease by either dividing (proliferating), or by migrating, allowing them to metastasize. When cancer cells adopt an EMT program to promote their migration, they generally stop dividing. The research findings indicate 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.

“We found that EMT program suppressed drug transporter and concentrative proteins, which inadvertently protected these cancer cells from anti-proliferative drugs such as gemcitabine,” said Kalluri, chair of Cancer Biology. “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.

Study findings were published in the online version of Nature.