"Although we are well aware that every cancerous tumor is a collection of different cells, the tendency is to treat it as if it were made of one piece," says Dr. With me Tirosh, who recently joined the Weizmann Institute. "As a result, drugs that successfully eliminate most of the tumor sometimes leave some of its cells intact - and the cancer returns. If we look closely enough, we might be able to identify the characteristics of the surviving cells, and even locate their weaknesses." In this way, Tirosh offers a new angle for the study of cancerous tumors - as ecosystems in which each cell plays a different role.
Dr. Tirosh, a member of the Department of Molecular Biology of the Cell, applied this "ecological" approach already in his post-doctoral research at Harvard University and the Broad Institute, in the research groups of Prof. Aviv Regev and Prof. Todd Golub. During the research he began to use an extraordinarily powerful method: RNA sequencing of single cells in thousands of cells at once. Prof. Ido Amit from the department of immunology at the institute is one ofPioneers of this method. RNA sequencing - the genetic information in action - makes it possible to see what the cells are doing, and sequencing many cells at once gives researchers the ability to perform a detailed analysis of the "ecosystem" itself.
"This method allows us to ask questions such as: Which cells are likely to develop resistance to treatment? Which of them will lead to the development of metastases? Indeed, only a few of the tumor cells have the ability to leave the main site, migrate in the body, and adapt to new tissue"
Dr. Itai Tirosh. Uses new RNA sequencing methods to study the diversity of cancer cells. Source: Weizmann Institute magazine.
Dr. Tirosh and his colleagues use samples from tumors taken immediately after surgery, and the cells are immediately separated for their RNA sequencing. "This method allows us to ask questions such as: Which cells are likely to develop resistance to treatment? Which of them will lead to the development of metastases? Indeed, only a few of the tumor cells have the ability to leave the main site, migrate in the body, and adapt to new tissue," he says. This ability, he adds, is usually considered the result of mutations in the genes of cancer cells, but he believes that this is not the case in most cases. In fact, this is due to epigenetic changes - which do not change the genes themselves, but the control over them.
A study conducted in 2014, in which Dr. Tirosh and the members of the research group described the different cells in a deadly type of brain cancer - glioma, led toThe discovery of a small cell population Has certain similarities to neural stem cells, in addition to the two main types of cancer cells in these tumors. These findings supported the idea that glioma tumors contain cancer stem cells that survive chemotherapy and cause the cancer to recur. "We must identify these rare but deadly cells and learn to eliminate them," he says.
Immunohistochemical photographs of samples from head and neck cancer tumors in two patients. Colored in brown and red are early markers for the transformation of the cells in the outer margins into cells of a different type in preparation for migration in the body and the formation of metastases. Source: Weizmann Institute magazine.
בAnother study, which was based on tumor samples from melanoma patients, the research group characterized drug-resistant tumors, which seemed to lack a characteristic set of changes - a kind of "resistance software" - that scientists found in more aggressive types of drug-resistant tumors. The group discovered that these tumors actually have drug resistance "software", but only in a small number of cells. Dr. Tirosh points out that most of the methods used today for treatment are not sufficiently sensitive and do not allow these rare cells to be discovered, although it is possible that they are responsible for the development of resistance.
In his latest study, QReported in the scientific journal Cell, Tirosh and other researchers in the United States conducted an analysis of head and neck cancer samples, and showed that such a basic thing - as the location of the cell in the tumor - may have a decisive weight in the development of metastases in the future. Cells located on the outer margins of the tumor are often more likely to exhibit early epigenetic marks, which have taught that they can transform into a different type of cell - the same change that allows the cell to migrate through the body. This finding indicates the possibility of developing a way to stop the process during which such "end cells" become another type of cells before migration.
RNA sequencing of individual cells makes it possible to map the ecosystem of cancer cells. The cancer cells that are in the process of turning into other cells (in red) are found at the outer edges of the tumor. Source: Weizmann Institute magazine.
In his laboratory at the institute, Dr. Tirosh continues to collaborate with groups in the United States, as well as with hospitals in Israel, in order to examine individual cells in samples taken from patients. His lab also uses tissue culture models to reproduce the wide variety of cells that are present in patient samples. The scientists then examine how diversity is controlled, and discover the roles played by cells of different types within a mixed "ecosystem".
A family of researchers
Dr. Tirosh completed his master's and master's degrees at the Weizmann Institute in the research group of Prof. Naama Barkai in the Department of Molecular Genetics. He is married to Dr. Reot Shema, who did her doctoral research in the laboratory of Prof.Yadin Dodai in the neurobiology department. While waiting for Raot to finish her studies, he worked as an independent post-doctoral researcher at the Institute, after which the couple went with their two daughters to do post-doctoral research at the Broad Institute. Later, Reut became a scientific consultant for venture capital companies. Her twin sister, Dr Efrat heard, recently joined the institute's biological control department as a senior scientist.
