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.
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