Research shows new ways to curb the development anti-cancer therapy resistance

Reviewed by Kate Anderton, B.Sc. (Editor)Feb 5 2020

Research by Professor Yuval Shaked of the Technion - Israel Institute of Technology presents new ways to curb the development anti-cancer therapy resistance, a phenomenon that is detrimental to the efficacy of existing cancer treatments. His research and research of others that followed this route was recently summarized in a published article in Nature Reviews Cancer.

The background of the present article is the great challenge posed by resistance to anti-cancer therapies. Although the initial cancer treatment phase is often successful, many patients are affected by the development of resistance, characterized by tumor relapse and/or spread.

The majority of studies have so far focused on investigating the basis of resistance as a result of tumor-related changes. In the last decade, Prof. Shaked and his team have demonstrated the patient's "contribution" to this resilience. This direction has been a paradigm shift in understanding cancer recurrence, and encouraged the scientific and medical community to further advance its understanding how the body protects the cancer from the treatment. The current understanding is that cancer therapy can induce local and systemic responses in the patient's body, and these actually support the resurgence of cancer and its progression.

The article published in Nature Reviews Cancer discusses these processes and more importantly - presents an outline for therapy that will prevent the development of treatment resistance. The article suggests how this new information can be used in the clinic. Specifically, it proposes that identifying these new mechanisms of treatment resistance can help advancing the important global trend of personalized (precision) medicine.

Prof. Yuval Shaked is the head of the Technion Integrated Cancer Center and the chief scientific advisor of ONCOHOST – a company he founded that work on translating this specific research direction into clinical use that will eventually improve the current treatment of cancer patients.

Some of Prof. Shaked's discoveries in recent years have been linked to one of the most complex cancer therapy challenges: to understand why cancer therapy only helps some patients. The American Society of Clinical Oncology has defined the ability to predict patient response to treatment as an area of research of the utmost priority.

Prof. Shaked's research focuses on predicting, as early as possible, the patient's response to anti-cancer therapy, and improving existing treatments. He said, "current modern immunotherapy has revolutionized cancer care. However, despite considerable advances in cancer treatment, most patients do not respond to therapy at all or from a particular stage. Without the ability to predict the effectiveness of treatment, many suffer from disease recurrence or spread, which sometimes erupts with even greater violence. Over the years, many have investigated and are still investigating the effect of therapy on the tumor itself, but few have analyzed the effect of the therapy on the patient." Prof. Shaked's research shows that predicting the host response to therapy can significantly improve patient care.

This phenomenon of host response to therapy has been studied in the past by Prof. Shaked mainly in the context of chemotherapy, which harms not only cancer cells but also healthy cells in the body. But in a series of recent articles, Prof. Shaked found that this reaction occurs in almost every existing anti-cancer therapy, including advanced therapies such as biological therapy. The host's response to treatment involves the production of resources such as proteins and increased release of growth factors –processes that protect the tumor and allow it to flare up and metastasize.

We are not saying that existing treatments are not good. They just aren't suitable for everyone. As mentioned, each treatment triggers a host response, and when this response exceeds the therapy effect, we receive ineffective treatment. For the therapy to be effective at the specific host level, it is important to predict the same counter-response and try to block it. This is how we will gain much more effective therapy."

Professor Yuval Shaked, Technion - Israel Institute of Technology

The overall trend of the medical world today is personalized medicine – an approach that matches the optimal specific treatment to the actual patient. Personalized medicine exists today in practice, but it is still very limited in its capabilities.

"To improve personalized medicine, we need to understand the mechanisms of the disease in depth and plan the optimal patient care," said Prof. Shaked. "In the context of cancer, personalized medicine not only allows us to tailor a drug for the tumor but also to combine dedicated medications – a cocktail that is not based on empirical experience, but rather, on understanding the biological processes in the body that the therapy causes."

Prof. Shaked's research has already demonstrated the effectiveness of anti-cancer therapies based on the right combination of drugs, and may provide a good basis for personalized medicine in various therapies. "For immunotherapy, one of the most important effective approaches today in the field of cancer, only some 20-30% of patients today respond. Through blood testing, we can predict the outcome of patients treated with immunotherapy and continue such treatment only in patients in whom treatment is expected to be effective. Based on the present study, in the future we may offer combined therapies to increase the effectiveness of treatment or allow patients who are currently unresponsive to immunotherapy drugs to respond to them. This is a huge revolution that we must advance not only in research but also in the commercialization of research into actual therapies. Only then can we contribute to saving lives."

ONCOHOST is currently conducting clinical trials that measure the host's response to patient care and predicts the effectiveness of the treatment. The company is also looking for ways to integrate different therapies to increase treatment effectiveness.

"We have already reached clinical trials in Israel, and in advance-stage negotiation to implement such a trial in additional countries in Europe and the United States, on the way to turning these said discoveries into the correct diagnostics and innovative medical care," said Prof. Shaked. "The transition from basic laboratory knowledge to the patient's bed must undergo many stages of feasibility, regulation, and therapy effectiveness. These actions are not conducted in the laboratory, but mainly by pharmaceutical companies, who are able to take scientific findings to clinical realization in patients. According to the clinical trials, we estimate that based on a simple blood test, we will be able to provide the patient with up-to-date information about the expected efficacy of the therapy being received and the options to modify it to improve outcomes."