A shortcut to preventing cancer - SCIENCETINE

 

Finally.. A shortcut to preventing cancer!

 

According to a recent theory, mutations have a few simple means of establishing themselves in cells and causing tumors. The road to cancer prevention is lengthy and tough for many researchers, but a recent study by Rice University scientists reveals that there may be shortcuts.

Rice scientist Anatoly Kolomeisky, postdoctoral researcher Hamid Teimouri, and research assistant Cade Spaulding are working on a theoretical framework that will explain how tumors caused by a variety of genetic alterations might be better identified and possibly prevented.

          

(Authors are, from the left, Cade Spaulding, Anatoly Kolomeisky and Hamid Teimouri

 Credit: Rice University)

 This is accomplished by recognizing and disregarding transition pathways that do not contribute significantly to the fixing of mutations in a cell that subsequently forms a tumor.

The report, which was published in the Biophysical Journal on May 13th, 2022, describes their investigation into the effective energy landscapes of cellular transformation pathways linked to a number of cancers. The capacity to narrow down the number of pathways to those that are most likely to initiate cancer could aid in the development of techniques to interrupt the process before it begins.

“In some sense, cancer is a bad- luck story”said Kolomeisky, a chemistry and chemical and  biomolecular engineering professor. “We think we can decrease the probability of this bad luck by looking for low-probability collections of mutations that typically lead to cancer. Depending on the type of cancer, this can range between two mutations and 10.”

The effective energies that regulate interactions in biomolecular systems can be used to predict how they will behave. The theory is extensively used to predict how a protein would fold based on the sequence and interaction of its constituent atoms.

 The Rice team is applying the same concept to cancer start pathways that operate in cells but may contain alterations that escape detection by the body's defenses. When two or more of these mutations are fixed in a cell, they are passed down to the next generation when the cells split and tumors form.

(A Rice University algorithm identifies and disregards transition pathways that don't contribute much to the fixation of mutations in a cell that goes on to form a tumor. Credit: Hamid Teimouri/Rice University)

According to Kolomeisky's calculations, the chances favor the most dominant routes, which move mutations forward with the least amount of energy expended.

“Instead of looking at all possible chemical reactions, we identify the few that we might need to look at,” he explained. “It seems to us that most tissues involved in the initiation of cancer are trying to be as homogenous as possible. The rule is a pathway that decreases heterogeneity is always going to be the fastest on the road to tumor formation.”

The enormous number of possible paths appears to make reducing them down an impossible task.

“But it turned out that using our chemical intuition and building an effective free-energy landscape helped by allowing us to calculate where in the process a mutation is likely to become fixated in a cell,” Kolomeisky said.

The researchers started by focusing on pathways with only two mutations that, when corrected, cause a tumor to form. More mutations, according to Kolomeisky, will make calculations more complicated, but the technique will remain the same.

 Much of the credit for this goes to Spaulding, who developed the algorithms that significantly simplify the calculations under Teimouri's guidance. When the visiting research assistant approached Kolomeisky for advice, he was just 12 years old. He joined the Rice lab last year at 16 and will attend Trinity University in San Antonio this autumn, having graduated two years early from a Houston high school.

“Cade has outstanding ability in computer programming and in implementing sophisticated algorithms despite his very young age,” Kolomeisky said. “He came up with the most efficient Monte Carlo simulations to test our theory, where the size of the system can involve up to a billion cells.”

Spaulding said the project combined his interests in chemistry, physics, and biology with his computer programming talents in a way that he enjoys.

“It was good way to combine all of the branches of science and also programming, which is what I find most interesting,” he said. The research builds on a report published in 2019 in which the Rice group studied stochastic (random) processes to figure out why some cancerous cells manage to overcome the body's defenses and spread the disease. But, according to Kolomeisky, understanding how those cells become cancerous in the first place could help prevent them from becoming cancerous in the first place. “This has implications for personalized medicine,” he said. “If a tissue test can find mutations, our framework might tell you if you are likely to develop a tumor and whether you need to have more frequent checkups. I think this powerful framework can be a tool for prevention.”

The Welch Foundation (C-1559), the National Science Foundation (1953453, 1941106) and the NSF-supported Center for Theoretical Biological Physics (2019745) supported the research.

 

Reference: “Optimal pathways control fixation of multiple mutations during cancer initiation” by Hamid Teimouri, Cade Spaulding and Anatoly B. Kolomeisky, 13 May 2022, Biophysical Journal.

2022-06-23