The University of Texas Health Science Center at Houston (UTHealth) has received a grant worth $3,481,666 from the State of Texas to fund research into novel therapies to treat the most fatal cancers, such as pancreatic, colon and lung cancer. The studies on molecular mechanisms will be supported through the Cancer Prevention & Research Institute of Texas (CPRIT).
The three-year grant was awarded to UTHealth in order to fulfill the need for new discoveries, as well as to accelerate the study of the molecular mechanism that is thought to be responsible for about 400,000 new cases of cancer in the United States every year, as announced by the university in a press release. Cancer is a disease characterized by uncontrolled growth of cells due to cell signaling collapses associated with molecular switches.
The failure of those molecular switches may mean the trigger of cell growth as well as division, one of the most common ones being the K-Ras protein. In approximately 20% of the cases of human tumors, a mutated version of the K-Ras is present. Therefore, the scientists plan to invest the two funding grants to explore new compounds able to treat those types of cancer, and to measure their effectiveness.
“K-Ras is mutated in more than 90 percent of pancreatic cancers, 50 percent of colon cancers and approximately 25 percent of non-small cell lung cancers,” explained the chairman of the Department of Integrative Biology and Pharmacology at the UTHealth Medical School, John Hancock, MB, BChir, Ph.D., ScD.
Hancock, who was awarded a $1,511,840 grant, is analyzing an obsolete antianginal agent used in Europe in the 1980s called fendiline in order to improve the medication designed as anti K-Ras and its effectiveness. The scientist expects to be able to test already improved versions of the compound in a mouse model of pancreatic cancer.
“The purpose of this project is to improve the K-Ras inhibitor function of fendiline by modifying the molecule and synthesizing new chemical derivatives,” Hancock said. “These studies will lead to the identification of more potent anti K-Ras drugs that are ready for evaluation in patients with pancreatic cancer.”
Alemayehu “Alex” Gorfe, Ph.D., and John Putkey, Ph.D. are the co-principal investigators for another research project that was awarded $1,969,826 in funding, which is focused on screening millions of compounds through computer simulations. The researchers are planning to conduct biophysical and cell biological studies, with the goal of developing new therapy options able to inhibit the mutant forms of K-Ras activity.
“We have decided to attack this elusive foe by assembling a team of experts from diverse fields and adopting a strategy that integrates theoretical biophysics, computational simulations, and high-end nuclear magnetic resonance as well as other biophysical and biological approaches,” stated Gorfe, who is an associate professor in the Department of Integrative Biology and Pharmacology at the UTHealth Medical School.
In addition, Putkey, who serves as professor in the Department of Biochemistry and Molecular Biology at the UTHealth Medical School, said: “I would hope at the end of this project we would have several promising lead compounds that could be developed into drugs that inhibit the biological activity of mutated K-Ras.”
Gorfe had already been responsible for a research that used supercomputer simulations to demonstrate that Ras proteins cluster together, forming aggregates that distort the cell membrane, a discovery that was crucial for the further studies regarding cancer treatments and anti K-Ras drugs.
This time, he believes that “the work will advance laboratory discoveries to clinically and commercially viable outcomes, which will break new grounds in cancer therapy with profound benefit to millions suffering from the many diverse K Ras-related carcinomas,” added Gorfe.