Scientists discover new carcinogenic mechanism, develop new drug to treat it

Another important step in the fight against cancer was made possible thanks in part to the research of scientists at BYU. Dr Josh Andersen, who heads the university’s Fritz B. Burns Cancer Research Lab, has discovered the mechanism by which a gene called TNK1 becomes an oncogenic driver of cancer. TNK1 is present in all cells, but once mutated it becomes dangerous and able to convert normal cells into cancer cells. This places TNK1 in a selected category of genes responsible for cancer.

“You can think of the engines of cancer as the engine that makes cancer grow and progress,” Andersen said. Andersen and his colleagues also discovered how mutations in the TNK1 gene cause cancer. This is an important finding given that only a handful of other pilots like TNK1 are known to scientists.

“One of the biggest modern challenges in cancer research is to identify new drivers of cancer, because each holds the key to potentially much more effective cancer treatment,” said Andersen.

For years, Andersen has studied a cancer-promoting protein called 14-3-3 that exists at unusually high levels in cancer cells. Six years ago, he identified TNK1 as a 14-3-3 interaction partner. His research, along with that of Dr. Jeff Tyner of Oregon Health Sciences University, has shed new light on TNK1 and how it works as a driver of cancer. Andersen, Tyner and other scientists, including Drs. BYU’s Ken Christensen and James Moody shared research and data in a recently published article in the scientific journal Nature Communication.

After identifying TNK1 six years ago, Andersen and several Ph.D. students began working to understand its properties with the aim of designing and developing a new drug to treat tumors caused by TNK1.

“Targeted therapy is the goal here,” Andersen said. “Being able to offer cancer therapy that targets only the engine of cancer – the engine that makes cancer grow – will help people live longer, healthier lives without cancer. Targeted therapy promises to be much more effective with fewer side effects than traditional chemotherapy and revolutionizes cancer treatment. “

But developing drugs that target cancerous tumors is not easy; in fact, it could be the most difficult task that scientists face, especially in an academic setting. This did not deter Andersen or his students. Andersen contacted Dr. Steve Warner, senior vice president and head of U.S. research at SDP Oncology, an international company that discovers and develops cures for cancer with a branch in Lehi, Utah, and he asked for help in developing a drug to target TNK1.

Warner, an undergraduate BYU classmate from Andersen, was excited about the prospect of working together again.

“Back when we were students at BYU, we became friends and bound by a common interest in wanting to pursue further education and careers in biomedical research,” Warner recalled. “We parted ways after BYU and went to graduate school in different places, but eventually we both found our way back to Utah. Working on this drug development project for TNK1 was our first collaboration. “

While it’s never easy to develop a drug, the years of research and data Andersen shared with SDP Oncology gave their researchers a great place to start. Scientists at SDP Oncology began to design compounds that would target TNK1 in cancer cells. Using computer modeling and rational structure-based design, they continued to test and then optimize the reaction of this compound.

“We didn’t just design a drug and say, ‘Here it is! “” said Warner. “Through trial and error, we would design and synthesize 20 or 30 potential drug candidates, then evaluate those with different lab experiences. The results of these studies have helped us understand how to improve the drug’s interaction with TNK1 and how to balance the need. to retain other properties required for a viable drug. We went through these iterative cycles of optimization until we identified a drug that we could move forward with. “

The preclinical results for the drug, called TP-5801, are extremely promising and have both Andersen and Warner optimistic about future development.

“We were very surprised at how quickly we were able to find and optimize a development candidate for TNK1, which was made possible by research already done by Dr. Andersen,” said Warner. “Preclinical data shows the drug to show great promise with deep activity in cancer models driven by TNK1. “

The compound has passed the steps required by the FDA and is now ready for what is called a first human study or a Phase 1 clinical trial.

Current BYU doctorate. student Chrissy Egbert and Ph.D. graduate, Dr Tsz-Yin Chan, along with a team of undergraduate researchers, have worked on TNK1 alongside Andersen for the past six years and are delighted to see their work relentlessly published.

“I started working on this project six years ago,” Chan said. “We almost gave up on this project after the first two years because we continued to find ourselves in dead ends. I’m so glad we tried some creative experiments and made a breakthrough.”

Egbert says the opportunity to get involved in meaningful research while in graduate school was an experience she had never had before.

“Before attending BYU, I had very little exposure to doing real, relevant research,” Egbert said. “It has been a really exciting experience to be a part of the TNK1 project, being able to discover unknown information and connecting pieces to begin to understand TNK1 and its role in cancer has extended my knowledge and my abilities. all the opportunities BYU gave me during my PhD. ”