Drug used for cocaine addiction could pave the way for new treatment for advanced colon cancer

A cutting-edge new study from the University of Ottawa (uOttawa) has found that vanoxerine, a drug originally developed for the treatment of cocaine addiction, could hinder advanced colorectal cancer stem cells by essentially rewiring genetic networks reviews.

This new research published in Natural cancer led by Dr. Yannick Benoit, principal investigator and associate professor in the Department of Cellular and Molecular Medicine (Faculty of Medicine) at the University of Ottawa, revealed that vanoxerin plays a completely unexpected mechanism in cancer.

Investigators observed that vanoxerine is potent when it suppresses the activity of cancer stem cells in the tissues of colon cancer patients and in tumors implanted in laboratory animals. It interferes with a protein that transports dopamine, the brain chemical involved in feelings of pleasure and reward, and represses an enzyme called G9a in colorectal tumors.

“Notably, tumors treated with vanoxerine become more susceptible to attack by the immune system due to the reactivation of old viral DNA fragments accumulated in our genome throughout evolution. This finding is quite significant, given that colorectal tumors tend to show a poor response to standard treatments. immunotherapy,” says Dr. Benoit, who was one of six national winners in the 2022 Gairdner Foundation Early Career Investigator Competition.

A silent killer

Colorectal cancer, when cells grow and divide uncontrollably in the colon or rectum, is the second leading cause of cancer-related deaths worldwide and is considered a “silent cancer” because it usually does not cause symptoms in the early stages. Although risks increase with age, new statistics show an alarming increase among young adults.

Because it is frequently diagnosed in advanced stages when treatment options are few, it is imperative to discover new methods to ward off colorectal cancer cells and tumors. When searching for a drug that was tested safely in patients, the most promising option turned out to be vanoxerine, a dopamine reuptake inhibitor.

The research team observed such minimal toxicity from vanoxerine treatments in tests on healthy human and mouse tissues that Dr. Benoit says their work could potentially provide “a safe way to eliminate cancer stem cells colorectal tumors without harming the body’s “good stem cells.”

A new and promising treatment

Although prevention and early detection remain the best weapons against colorectal cancer, these very convincing discoveries could pave the way for a promising new therapeutic option for patients battling advanced disease.

“For those unfortunate enough to suffer from advanced and aggressive forms of colorectal cancer, we sincerely hope that our work can lead to the development of powerful treatment options in the future and significantly increase their chances of survival,” says Dr. Benoit.

The roots of collaboration

The study was highly collaborative and benefited from the expertise of the broad research ecosystem of the University of Ottawa Faculty of Medicine.

The first author is Christopher Bergin, a recent doctoral student. graduate from Dr. Benoit’s laboratory who methodically tested vanoxerine for its anticancer stem cell properties in patient-derived organoids. Dr. Rebecca Auer, scientific director of the Cancer Therapy Program at the Ottawa Hospital, provided access to tissue from colorectal cancer patients. Dr. Mario Tiberi and Dr. Michele Ardolino provided essential information and expertise.

While working on this study, Dr. Benoit’s laboratory hosted Dr. Tanguy Fenouil, a French gastrointestinal pathologist whose collaborative work was essential.