A Technion researcher presents new ways to curb the development of resistance to cancer treatments

Prof. Yuval Shaked is the head of the Integrated Center for Cancer Research at the Rappaport Faculty of Medicine at the Technion and the chief scientific advisor of ONCOHOST - a company that works to translate its research into clinical use to improve the treatment of cancer patients.

A study by Prof. Yuval Shaked, head of the Integrated Center for Cancer Research at the Rappaport Faculty of Medicine at the Technion, presents new ways to curb the development of resistance to anti-cancer treatment - a phenomenon that impairs the effectiveness of existing cancer treatments. The study was recently published in the prestigious journal Nature Reviews. The background to the current article is the great challenge posed by resistance to anti-cancer treatments. Although the initial phase of cancer treatment is successful in many cases, many patients are harmed by the development of resistance, which is characterized by the re-emergence and/or spread of the tumor.

Most studies on the issue of resistance have so far focused on the development of resistance as a result of changes in the tumor itself. Only in the last decade has the scientific and medical community examined the patient's own "contribution" to this resistance. Today there is evidence that cancer treatment may cause local and systemic reactions in the patient's body, and these actually support the re-emergence of the cancer and its spread.

The article published in Nature reviews discusses these processes and more importantly - presents a therapeutic outline that will prevent the development of resistance to treatment, and this in accordance with the important global trend of personalized medicine.

Prof. Yuval Shaked is the head of the Integrated Center for Cancer Research at the Rappaport Faculty of Medicine at the Technion and the chief scientific advisor of ONCOHOST - a company that works to translate its research into clinical use to improve the treatment of cancer patients.

Some of Prof. Shaked's discoveries in recent years are related to one of the most complex challenges in the field of cancer treatment: understanding why cancer treatment only helps some patients. The American Society of Clinical Oncology has defined the ability to predict patients' response to treatment as a top priority research area.

Shaked's research focuses on predicting as early as possible the patient's response to the anti-cancer treatment and improving the existing treatments. According to him, "Chemotherapy treatments, targeted biological treatments as well as immunotherapy treatments have made a huge revolution in the field of cancer treatment, and are effective in many cases both in damaging the primary tumor and in treating cancer metastases. However, despite the considerable progress in cancer treatment, most patients do not respond to treatment at all or to a certain stage. Without being able to predict the effectiveness of the treatment, many of them suffer from a recurrence of the disease, which sometimes erupts even more violently. Over the years, many researchers have studied the effect of the treatment on the tumor itself, but only a few have analyzed the effect of the treatment on the patient himself. Shaked's research indicates that predicting the body's response to treatment (host response) may significantly improve patient treatment."

This phenomenon of the body's response to treatment was studied in the past by Prof. Shaked mainly in the context of chemotherapy treatments, which damage not only the cancerous cells but also healthy cells in the body; However, in a series of articles from the last few years, Prof. Shaked found that this reaction occurs in almost every existing anti-cancer treatment, including advanced treatments including biological therapy and immunotherapy. The body's response to treatment includes the production of resources such as proteins and the increased release of growth factors - processes that protect the tumor and allow it to flare up again and metastasize.

"It is important to me that it should not be implied that the existing treatments are not good," emphasizes Prof. Shaked. "They just don't suit everyone. As mentioned, every treatment leads to a host response, and when this response outweighs the therapeutic effect, we will receive an ineffective treatment. In order for the treatment to be effective at the level of the specific patient, it is important to predict the same counter-reaction and try to block it. This way we will benefit from a much more effective treatment."

The overall trend in the world of medicine today is personalized medicine - an approach that adapts the optimal specific treatment to the patient. Personalized medicine exists today in practice but is still very limited in its capabilities. "In order to improve personal medicine, we must deeply understand the mechanisms of the disease and plan the optimal treatment for the patient. In the cancer context, personalized medicine allows us not only to adapt a drug to the tumor but also to put together a dedicated combination of drugs - a cocktail that is not based on empirical experience but on an understanding of biological processes in the body, which the treatment stimulates."

Prof. Shaked's research has already demonstrated the effectiveness of anti-cancer treatments based on a correct combination of drugs and may form a good basis for personalized medicine in various treatments. "Today, only about 20% of patients respond to immunotherapy - one of the most important and effective approaches in the field of cancer today. Through a blood test we can predict the body's reaction to the immunotherapy treatment and perform such treatment only in patients in whom the treatment is expected to be effective. Based on the current research, in the future we will be able to offer combined treatments to increase the effectiveness of the treatment or allow patients who currently do not respond to the immunotherapy drugs to respond to them. This is a huge revolution that we must promote not only in research but also in the commercialization of research for actual treatments. This is the only way we can contribute to saving lives."

Today, the company conducts clinical trials in which it measures the body's response to the treatment of patients and predicts the effectiveness of the treatment. ONCOHOST is also looking for ways to combine different treatments to increase the effectiveness of the treatment. "Thanks to the company we founded, we have already reached clinical trials in Israel, and in the near future we will also conduct trials in England and the United States, on the way to turning the said discoveries into correct diagnostics and innovative medical treatment. The transition from the basic knowledge in the laboratory to the patient's bedside must go through many stages of feasibility, regulation and testing the effectiveness of the treatment. These operations are not done in the laboratory but mainly by the pharmaceutical companies, which have the power to take the scientific findings into clinical use in patients. According to the clinical trials, we estimate that with a diagnosis based on a simple blood test, we can provide the patient with updated information about the expected effectiveness of the treatment he is receiving and the possibilities of changing it to improve the results."

For the article in the journal Nature Reviews click here