In Dr. Yuval Shaked's laboratory, for several years, they have been trying to understand how cancerous tumors manage to escape conventional treatment, and why cancerous tumors grow or develop resistance to different types of treatments
Researchers from the Rappaport Faculty of Medicine at the Technion and Utrecht University in the Netherlands have shown that chemotherapy drugs, beyond their ability to kill tumor cells, are also capable of increasing the risk of a metastatic process in mice. Several different mechanisms have been proposed to explain the metastatic process after chemotherapy, and it is possible that these mechanisms exist simultaneously. Dr. Yuval Shaked from the Technion and Professor Emil West from Utrecht University published their findings in the scientific journal CANCER RESEARCH
In Dr. Yuval Shaked's laboratory, for several years, they have been trying to understand how cancerous tumors manage to escape conventional treatment, and why cancerous tumors grow or develop resistance to different types of treatments. In contrast to other studies conducted in this field, where the cancer cells themselves and their ability to develop resistance to treatment are usually tested, in this laboratory the focus is on a different field: the working hypothesis is that in addition to the changes that apply within the cancer cells following the treatment, other cells in the shelter itself, that is, in the human body, change, and are actually able to contribute to cancer growth, and the development of resistance to treatment. In other words, the tumor "calls" for help after treatment, and the body's cells are mobilized to help it.
In fact, already several years ago, this group showed that the process of creating new blood vessels in cancer, which is a critical process in tumor development, becomes aggressive precisely after anti-cancer treatment, for example after chemotherapy treatment. The creation of new blood vessels in cancer has been a known process for years, but in previous studies by this group it was found that the process of creating cancerous blood vessels occurs significantly and intensively after various chemotherapy treatments. As a result, the (at least partial) success of treatments that damage new blood vessels can be explained only when they are combined with different chemotherapy treatments, but not when they are given alone. This work, which was published several years ago in the scientific journal CANCER CELL, led Dr. Shaked's laboratory to continue researching the relationship between anti-cancer treatment and coping with cancer in the various stages of treatment - coping that requires the help of different cells that are in the shelter.
Recently, two articles published in the journal CANCER RESEARCH by two separate research teams - one from the Technion (Dr. Yuval Shaked), and the other from Utrecht University in the Netherlands (Professor Emil West) - showed that chemotherapy drugs, in addition to their ability to kill tumor cells, are also able to increase the risk of a metastatic process in mice. Several different mechanisms have been proposed to explain the metastatic process after chemotherapy, and it is possible that these mechanisms exist simultaneously.
Dr. Svetlana Gingis-Vlitsky, the leader of the research from the Technion, showed that plasma from mice treated with chemotherapy drugs causes cancer cells to go through a process similar in form to a metastatic process. She found that one of the reasons for this phenomenon is the activation of various bone marrow cells that reach the cancerous tumor and secrete enzymes that break down the intercellular matrix, thereby contributing to the invasiveness of the cancer cells and their mobility within the tissue until they reach other areas, i.e. metastases. When she used substances or drugs that neutralize the same enzymes, the chemotherapy treatment did not cause the development of metastases.
These findings imply that chemotherapy has negative side effects not only in terms of the toxicity of the drug, but is also able to increase factors that contribute to the processes in the reservoir that result in a significant contribution to the tumor cells, and it is very possible that these effects contribute to a reduction in the effectiveness of the chemotherapy treatment in patients. In various clinical studies it was found that sometimes drug treatment against cancer can indeed help in significantly reducing the size of the primary tumor that developed, but for some reason the patient's life is not always prolonged despite the use of the drug. It is possible that the release of various substances from the warehouse, as described in these works, contribute to a metastatic cancer process that harms the patient and does not allow for life extension.
Dr. Yuval Shaked, who is in charge of the research, said that "if we find the same factors secreted from the reservoir that contribute to the growth of cancer after chemotherapy treatment, then we will have new tools and new targets in cancer that we have not known so far. Blocking those factors in combination with conventional treatment, namely chemotherapy, can significantly increase the success of this treatment."
Dr. John Ivos from the Department of Medicine at the Roosevelt Park Cancer Institute agreed that the findings of the two studies are important and can explain why the effect of chemotherapy is limited in certain patients and more importantly how the effectiveness of this treatment can be improved.
Prof. Sara Rocktinge from the Stanford-Burnham Institute for Medical Research said: "I hope that these articles will encourage more studies that examine the mechanisms of the formation of metastases that are formed as a result of chemotherapy and consider combined treatment in light of these mechanisms, because doctors will not stop using chemotherapy."
Indeed, Dr. Shaked's laboratory, in conjunction with a number of hospitals in Israel and the world, especially the Rambam Hospital in Haifa and the director of the oncology system Prof. Avraham Koten, the Emek Hospital in Afula (Dr. David Luban), as well as the European Oncology Hospital in Milan , Italy (Professor Francesco Bertolini) are working together to examine whether these alarming results found in mice do indeed appear in the clinic in a significant way, and if so, whether these factors can be used to predict which patients will benefit from one or another chemotherapy treatment.
Also, students, post-doctoral students, and the employees of Dr. Shaked's laboratory - Dr. Ella Parmeder, Tali Voloshin, Rotem Beril, Dror Eliskevic, Michal Munster, Liat Benyon, Valeria Miller - are currently working on finding additional components of a shelter that may be related to the aforementioned results. "We are in the process of establishing a consortium to continue the research of the metastatic effects of chemotherapy drugs and to identify new targets for treatment," said Dr. Shaked. "The consortium currently includes academic teams and private companies from Sweden, Greece, France, Germany, Ireland, Italy, and of course the Technion in Israel."
