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Proteins in the cancer network

Researchers are trying to find treatments adapted to protein networks that characterize cancer tumors

The field of clinical oncology and laboratory research has focused in recent years on developing methods that will lead to personalized cancer medicine. Prof. Nathalie Kravchenko-Balesha from the Laboratory of Biophysics and Cancer Research in the Faculty of Dentistry at the Hebrew University and her team investigate the molecular difference between cancer patients or between cancer cells and its translation into personalized drug combinations. Their goal is to characterize the cancerous tissue and predict how it will react to environmental changes and which drug combination will be the best and most effective for the patient.

What is the question? How to characterize cancer protein networks, to treat patients in a personalized way?

The cancer tumor proteins are organized within protein networks (pathways) that are unique to each patient, which during the course of the disease do not necessarily remain dependent on the mutations that caused it. They respond to changes that occur within the tumor or in its surroundings and cause the cancerous tissue to go out of balance, which may lead to interactions between the proteins that may vary from patient to patient. Information that flows through the protein networks, signals to the cancer cells whether to continue dividing without control, live or die, and is also unique to each patient or subgroup of patients and therefore requires personalized treatment. Dr

According to Prof. Kravchenko-Belsha, "the evolution of cancer cells is sophisticated and often utilizes existing pathways in the organism (for example cellular movement) to spread and survive. Although the mutations and molecular changes that are acquired in the disease and cause the tissue to go out of balance may vary from person to person, the result is similar: it allows the cancer cells to divide, compete and aggressively affect their environment, including healthy cells. Therefore, if we decipher all the protein networks operating in each and every tumor and know how to damage the central nodes with specific drugs, we can 'turn off' the flow of information in them, so that the cancer cells will not continue to divide, send metastases, survive or develop drug resistance. On the other hand, if we miss one or more of them, the information will continue to flow and the cancer cells will be able to survive and even change their identity. That is why we strive to understand what characterizes each and every network in each patient and how it is possible to damage them all."

If we decipher all the protein networks that operate in each and every tumor and know how to damage the central nodes with specific drugs, we can turn off the flow of information in them, so that the cancer cells do not continue to divide, send metastases, survive or develop drug resistance.

In a series of recent studies, with the help of a grant from the National Science Foundation, Prof. Karavchenko-Balsha and her team examined samples taken from human cancer tumors in the oral cavity, lungs, breast and skin. Hundreds of proteins known to be involved in cancer and protein networks were measured in each sample. Most of them were phosphorylated proteins (a sign that they are active). For example, they discovered that in some types of cancer, the EGFR protein (a factor in the growth, differentiation, movement and division of cells), and the ERK protein (it also plays an important role in a variety of cellular processes, including cell proliferation, cell survival and apoptosis - programmed cell death), belong to the same protein network , as previous studies also found. In contrast, in other types of cancer, they became disconnected or separated and participated in different protein networks. This is how the researchers concluded that there are patients for whom the anti-EGFR drug will not necessarily affect them because it will not also inhibit ERK. In addition, they concluded that there are tumors in which these proteins have no role and in their place other protein networks operate that require different treatment.

Later, the researchers performed experiments in which they implanted the tumor samples with high expression of EGFR and ERK in animals. After that, some of them were treated with combined treatment - an anti-EGFR drug and an anti-ERK drug - and some were treated with only one of the two drugs. It was found that the combined treatment effectively inhibited the tumors in which EGFR and ERK were separated and operated in different networks. The second treatment inhibited only part of the networks that worked in the tumor and was therefore less effective. When the tumors involved other networks (ie without ERK or EGFR), the treatment had no effect at all.

This is how the researchers showed that the most effective treatment is the one that is precisely adapted to the unique protein networks of each patient. Today they are testing whether personalized treatments also contribute more to the activation of the immune system - which may also be inhibited by the protein networks.

Life itself:

Natalie Kravchenko-Belsha

Dr. Nathalie Kravchenko-Balsha, married + son and daughter (twins aged 15.5), lives in the village of Oriya. She began the scientific-academic track and mainly cancer research after her mother died of the disease. She likes to travel with her family in Israel and abroad, read and watch plays and dance performances ("Before science, I dreamed of being a dancer. Today my daughter dances and we go to concerts together").

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