Israeli startup ONCOHOST is working on a blood test that can predict which cancer patients will respond to which treatment, and thereby figure out how to adjust prescribed therapies to prevent the recurrence of tumors.
The firm is conducting clinical trials to measure the blood test’s success in forecasting the effectiveness of a particular treatment on a particular patient. The company also hopes that information revealed by the blood test will help physicians decide what drugs should be integrated into the treatment to increase its effectiveness.
The work is based on a decade of research by Prof. Yuval Shaked of the Technion — Israel Institute of Technology. Shaked, who founded ONCOHOST and is its chief scientific adviser, is also head of the Technion Integrated Cancer Center, set up in 2016 to combine the knowledge in oncology accumulated at the Technion and its affiliated medical centers.
Shaked’s work has pioneered a new field in cancer research that looks not only at how the tumor cells of patients react to cancer treatment but at how the patients themselves react to a wide variety of therapies, demonstrating the body’s “contribution” to tumors’ possible resilience.
This research direction has created what the Technion says is a “paradigm shift” in understanding cancer recurrence, and has encouraged others in the scientific and medical community to further study how the body protects the cancer from treatment and can actually support its resurgence and its progression.
The aim of Shaked’s research and that of others is to find new ways to curb the development of a patient’s resistance to cancer treatment, a phenomenon that is detrimental to the efficacy of existing cancer medications and is a great challenge to cancer patients and researchers globally.
Indeed, although cancer treatment is often initially successful, many patients suffer from the development of therapy resistance, characterized by a tumor relapse and/or the spread of the tumor.
Cancer research so far has focused on investigating resistance through studying cells and tumor-related changes, Shaked said in a phone interview.
“In the last 50 years most of the research focused on the internal mechanism of the cancer cells that develop the resistance,” he said. Sometimes, the tumor cells are able to evade the drug or interfere with its activity.
With his lab’s work, Shaked said “we showed that this is only one side of the coin. The other side of the coin, surprisingly I would say, is our body,” which actually helps the tumor to “recover” from the initial impact of the drug that is meant to destroy it.
That’s because when a healthy person is injured, the body gears up to help repair the damaged tissue. Thus, when tumor cells are targeted by a cancer treatment — which causes damage to the tumor tissue — the body’s reaction is to go and repair the damage, not being able to discern between healthy cells and tumors.
“Our body helps the tumor recover from the damage we caused” with the drug,” he said. “The body doesn’t recognize the tumor as not part of its own.”
Mapping out responses
What Shaked’s team identified in its research is the different biological ways in which patients react to the various cancer treatments.
Shaked recently published a summary of his and others’ research that followed this path of study in Nature Reviews Cancer, listing the different host responses and reactions that take place as part of the body repair mechanism. For example, the patient could promote the formation of blood vessels in tumors, which help tumor cells grow, giving them oxygen and nutrients; or promote the quick regeneration of cells to replenish the ones that have been destroyed; or even develop metastatic growths, because motility is an important repair mechanism. All of these can be identified in the blood after the first cancer treatment, Shaked said.
The test the firm is developing takes blood from the patient before treatment and after the first cancer treatment, whatever it may be, and measures about 1,000 signatures of different plasma proteins.These proteins reveal the response pathways becoming dominant in the patient in reaction to the treatment, he said.
If the blood test shows that “the repair mechanism of the patient is very potent,” it means that the response to treatment won’t be good. But if the repair mechanism is slow and weak, the outcome will be much better, Shaked said.
These biological indicators can reveal if there is a potent or weak activity, which can then suggest whether the patient will benefit or not from the treatment, he said.
Shaked said that this means that alongside studying how the tumor reacts to the drugs, researchers and physicians should also study the host’s reaction to the treatment, which should become an important component of the treatment selected.
‘People now realize that this is an important issue that nobody looked at,” he said.
Furthermore, once it is known that a patient won’t react well to a specific treatment, ways to improve that treatment can be sought by teaming it with other drugs that could help it succeed.
For example, if a patient reacts by developing blood vessels, additional drugs could be administered to inhibit the blood vessel formation, helping the patient benefit from the treatment.
“On one hand we tell whether the patient will benefit or not from treatment,” he said. “The second thing will tell what could be complementary to the treatment in order to improve the outcome.”
“For the therapy to be effective at the specific host level,” it is important to predict the counter-response and try to block it, he said. “This is how we will gain much more effective therapy,” he said.
ONCOHOST is currently conducting clinical trials that measure the host’s response to drugs and predict their effectiveness. The company is also looking for ways to integrate different therapies to increase treatment effectiveness.
“We have already reached clinical trials in Israel, and are in advanced-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 Shaked. “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.”