Sub-cellular monitoring of malignant tumors

Researchers at the Technion believe their discovery of a new technology to monitor metabolic processes in cancerous tissue could lead to targeted drugs for preventing malignant growth.

Article by Kevin Hattori, published on American Technion Society on May 14, 2019.

Professor Tomer ShlomiProfessor Tomer Shlomi.

In recent decades, many studies have been conducted around the world on the development and spread of malignant tumors in the body, as well as their diagnosis and treatment. One of the most important discoveries is related to the unique metabolic properties of the cancerous cell.

Metabolism is a vital process that makes it possible for the cell to generate energy and produce the molecules needed for its development and survival. This process is very different in the malignant cell, as cancer cells divide uncontrollably, and their speedy growth reduces the oxygen and nutrients available to them and requires reprogramming of the metabolic processes. Successful monitoring of these metabolic changes could lead to the development of specific anti-cancer drugs that would impair the metabolic processes needed to sustain the cancerous tissue.

But applying this idea is not simple, because cellular metabolism is a very complicated process that involves the activity of thousands of genes and metabolic enzymes. Another major complication is that different areas of the cell maintain different metabolic processes, and existing technology does not allow each of them to be tracked separately.

Now, in a study published in Nature Communications, Professor Tomer Shlomi of the Technion Faculty of Biology and Computer Science and the Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering present a new technology for monitoring metabolic processes in different parts of the cell.

“We have developed a technique for monitoring the rate of metabolic reactions at sub-cellular resolution, particularly mitochondria and cytosol,” he said. Mitochondria are the cell’s “power station,” and cytosol is the fluid inside the cell.

Prof. Shlomi’s research group is an interdisciplinary team comprised of researchers from the fields of biology and computer science. The new technology also combines biological methods with computational methods, namely molecular biology and mass spectrometry, technology for identification of materials in a sample, along with decoding of measurements using computational analysis. This combination enables modeling of the metabolic processes at the sub-cellular level.

The new technology was used to study mutations that interfere with mitochondrial activity in cancer cells. To their surprise, the researchers discovered a unique backup mechanism that allows cancer cells to overcome mitochondrial mutation damage and survive through unknown metabolic activity, the reversal of the direction of the Krebs cycle, a major metabolic pathway involved in cellular respiration.

“This is the first time that a reversal of the activities of these enzymes has been observed in human cells and specifically in cancerous ones,” said Prof. Shlomi. “Understanding this reversal mechanism is paving the way for medical treatment that will neutralize it. In other words, drug targeting of this backup metabolic process enables to selectively kill the mutated cancer cells without harming the healthy cells.”

The study was supported by a grant from the European Research Council (ERC) and carried out with Dr. Alina Eisenstein and doctoral students Won Dong Lee and Dzmitry Mukha.