MINNEAPOLIS, MN- July 19, 2019 - For years, doctors and scientists have known very little about why patients can receive drugs successfully for months, or even years, before developing a drug resistance. New University of Minnesota Medical School research proposes that there is a cellular as well as molecular cause to this phenomenon in colon cancer, with potential application to other similarly aggressive cancers as well.
In a study published in Cancers, Emil Lou, MD, PhD, FACP, Assistant Professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, and his research team demonstrated that proteins derived from the oncogene KRAS have the ability to transfer between colon cancer cells via long cellular skyway-like extensions called 'tunneling nanotubes'.
KRAS is heavily implicated in driving cancer, including its origin and growth patterns in 30 percent of all cancers, and cancer becoming resistant to drugs. The study examined what happens when a normal form of the protein acquires a form that is mutant. It found that the transfer of KRAS causes the surrounding cells to behave in a more cancerous, invasive manner that is more likely to be resistant to standard drugs.
"Most aggressive metastatic colon tumors in patients will develop drug resistance. It's not a matter of 'if', but a matter of 'when' for most patients, and that's a big challenge in this field," said Dr. Lou. "We speculate that cutting off the line of communication for transfer of vital signals might be a novel therapeutic strategy in addition to standard-of-care chemotherapy."
Dr. Lou hopes that these findings will help devise better recognition of ways to revise clinical trial strategies to overcome biological resistance at the cellular level. "This study opens new avenues to fully understand the effects of the transfer of KRAS in colon and other similar cancers driven by KRAS," said Dr. Lou. Research into the next steps also will entail figuring out how to cut off that communication.
The first author of this study, Dr. Snider Desir, was a graduate student in the Department of Integrative Biology and Physiology at the University of Minnesota Medical School and performed this work during his graduate studies. This work was performed in collaboration with the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research in Frederick, Maryland and the Molecular Cytology Core Facility at Memorial Sloan-Kettering Cancer Center in New York, New York.
Direct link to the publication: https:/
Intercellular Transfer of Oncogenic KRAS via Tunneling Nanotubes Introduces Intracellular Mutational Heterogeneity in Colon Cancer Cells. Authors: Snider Desir, Phillip Wong, Thomas Turbyville, De Chen, Mihir Shetty, Christopher Clark, Edward Zhai, Yevgeniy Romin, Katia Manova-Todorova, Timothy K. Starr, Dwight V. Nissley, Clifford J. Steer, Subbaya Subramanian, and Emil Lou.
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