Scientists discover new cancer-causing mechanisms and develop new drugs to treat them

PhD graduate Dr. Tsz-Yin Chan has been studying TNK1 for the past six years with Professor BYU’s Dr. Josh Andersen and now has a vial of a new drug ready for clinical trials. Credit: Jaren Wilkey / BYU Photo

Thanks to research by BYU scientists, another important step in the fight against cancer has become possible. Dr. Josh Anderson, who heads the University’s Fritz B. Burns Cancer Institute, has discovered a mechanism by which a gene called TNK1 becomes a carcinogenic driver of cancer. Although TNK1 is present in all cells, it can be dangerous if mutated and can convert normal cells into cancer cells. This puts TNK1 into a selected category of cancer driver genes.

“Cancer drivers can be thought of as the engine that grows and advances cancer,” Andersen said. Andersen et al. Also elucidated how mutations in the TNK1 gene cause cancer. This is an important finding given that only a handful of other drivers like the TNK1 are known to scientists.

“One of the latest and greatest challenges in cancer research is identifying new cancer drivers, as each holds the key to potentially more effective cancer treatments,” Andersen said. increase.

For years, Andersen has been studying an abnormally high level of a cancer-promoting protein called 14-3-3 that is present in cancer cells. Six years ago, he identified TNK1 as an interaction partner for 14-3-3. His work, along with the work of Dr. Jeff Tiner of Oregon Health & Science University, has led to a better understanding of TNK1 and how it functions as a cancer driver. Both Andersen, Tiner, and other scientists, including Ph.D. BYU’s Ken Christensen and James Moody collaborated to share research and data in a recently published article in a scientific journal. Nature Communications..

After identifying TNK1 six years ago, he received several PhDs with Andersen.Students began working to understand their characteristics, with the goal of designing and developing new things. drag To treat tumors caused by TNK1.

“The goal here is targeted therapy,” Andersen said. “Being able to provide cancer treatments that target only the cancer driver, the engine that grows the cancer, helps people live longer and healthier lives without cancer. Targeted therapies have fewer side effects. We have a promise that it will be much more effective in. It is a traditional chemotherapy and is revolutionizing cancer treatment. “

However, developing drugs that target cancer tumors is not easy. In fact, it may be the most difficult challenge scientists face, especially in academic environments. It did not discourage Andersen and his students. Andersen contacted Dr. Steve Warner, Senior Vice President and Head of Research for SDP Oncology, an international company with a branch in Lehi, Utah, and asked him to assist in the development of drugs targeting TNK1.

Warner, a classmate at Andersen’s BYU department, was thrilled with the prospect of working with him again.

“When we were BYU students, we became friends and were connected through a common interest in pursuing further education and careers in biomedical research,” Warner recalled. “I broke up after BYU and worked in graduate school in various places, but eventually found a way back to Utah. It was the first time I worked together on this project to develop a drug for TNK1. . “

Scientists discover new cancer-causing mechanisms and develop new drugs to treat them

The preclinical results of this drug, called TP-5801, are very promising and both Andersen and Warner are optimistic about future developments. Credit: Jaren Wilkey / BYU Photo

Developing a drug is by no means an easy process, but years of research and data shared by Andersen with SDP Oncology have provided researchers with a great starting point. SDP oncology scientists have begun designing compounds that target TNK1 cancer cell.. Through computer modeling and structure-based rational design, they continued to test and optimize how this compound reacts.

“We didn’t just design one drug and say,’This is it!’,” Warner said. “By trial and error, we designed and synthesized 20 or 30 candidate drugs and evaluated them through various experiments in the lab. The results of these studies show how and needs to improve drug-TNK1 interactions. It helped me understand how to balance. To retain the other properties needed for a viable drug. We made these iterative optimizations until we identified a drug that could move forward. I repeated. “

The preclinical results of this drug, called TP-5801, are very promising and both Andersen and Warner are optimistic about future developments.

“We were very surprised that Dr. Andersen was able to quickly find and optimize TNK1 development candidates, which was made possible by the research he had already done,” Warner said. “Preclinical data show that the drug is very promising with profound activity in a model of cancer caused by TNK1.”

The compound has passed the procedures required by the FDA and is now ready for so-called first or phase 1 clinical trials in humans.

Current BYUP h.D. Student Clichy Egbert, PhD graduate Dr. Tsz-Yin Chan, and a team of undergraduate researchers have been working on TNK1 with Andersen for the past six years and are excited to see their efforts announced.

“I started working on this project six years ago,” said Chan. “After the first two years, I gave up on this project because it continued to be a dead end. I’m very happy to have tried some creative experiments and achieved a breakthrough.”

Egbert says that the opportunity to engage in meaningful research while working in graduate school was an experience she had never experienced before.

“Before joining BYU, I had few opportunities to do real-life related research,” says Egbert. “Participating in the TNK1 project was a really exciting experience. I was able to connect pieces to reveal unknown information and begin to understand TNK1 and its role. cancer I have improved my knowledge and abilities. I am grateful for all the opportunities BYU has provided to me in my PhD. ”

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For more information:
Tsz-Yin Chan et al, TNK1, is a ubiquitin-conjugating and 14-3-3-regulated kinase that can be targeted to block tumor growth. Nature Communications (2021). DOI: 10.1038 / s41467-021-25622-3

Quote: Scientists discover new cancer-driven mechanisms and develop new drugs to treat them (October 6, 2021), https: // Obtained from -mechanism-drug on October 6, 2021.html

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Scientists discover new cancer-causing mechanisms and develop new drugs to treat them

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