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

Article published at ats.org on February 4, 2020.

Anti-cancer therapy resistance: A devastating challenge

Although the initial cancer treatment phase is often successful, many patients become resistant to anti-cancer therapies, 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.

But over the last decade, Prof. Shaked and his team have shown that the patient’s body plays a role, too. They have discovered that cancer therapy can induce local and systemic responses in the body, and these actually support the resurgence of cancer and its progression.

Predicting resistance

Prof. Shaked’s research focuses on predicting a patient’s response to anti-cancer therapy. This prevents disease recurrence or spread, improving patient care and outcomes.

Most of Prof. Shaked’s research has been around patient responses to chemotherapy, which harms not only cancer cells but also healthy cells in the body. But his recent research suggests 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 metastasise.

Better, personalized treatments

Prof. Shaked emphasizes that his findings do not suggest that existing treatments are not effective. Rather, because each treatment triggers a response in a patient, it is important to match patients with the right treatments for their bodies.

For instance, only 20–30% of patients today respond to immunotherapy, one of the most important effective approaches currently in the field of cancer. Through blood testing, Prof. Shaked 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 his findings, in the future physicians may offer combined therapies to increase the effectiveness of treatment or allow patients who are currently unresponsive to immunotherapy drugs to respond to them.

Bringing this research from the lab to the bedside

Prof. Shaked is working with ONCOHOST, a company he co-founded, to commercialize his research. ONCOHOST is currently conducting clinical trials in Israel that measure the host’s response to patient care and predict the effectiveness of the treatment. They are in negotiations to implement clinical trials in additional countries in Europe and the United States.

The company is also looking for ways to integrate different therapies to increase treatment effectiveness.

Scientists have known that chemotherapy can damage the heart muscle. But what about the reverse — can heart disease impact cancer?

Article published at ats.org on July 14, 2020.

A research team led by Professors Ami Aronheim and Yuval Shaked of the Rappaport Faculty of Medicine at the Technion, with colleagues from Carmel Hospital, have found that early changes in the size, shape, or function of the heart caused by heart disease or injury, collectively known as cardiac remodeling, promotes cancer progression. The study, published in Circulation, demonstrates that catching and treating heart disease early on in cancer patients might help cardio-oncologists slow tumor progression and improve cancer outcomes.

“We recommend you treat heart problems early, when the body is still successfully coping with the problem, and not wait for a chronic condition,” said Prof. Aronheim. “Such problems can be detected with a simple echocardiography test, and in many cases, early catheterization may help to slow cancerous development.”

To mimic cardiac remodeling, the team exerted mechanical pressure on the heart of laboratory mice. The technique, known as transverse aortic constriction (TAC) stresses the mouse’s heart with a pressure overload resulting in an increase in heart cell growth that is common of cardiovascular complications in humans. The team then implanted cancer cells in the mice to see if the early cardiac changes affect tumor progression.

The researchers found the mice developed larger tumors at the site of the implanted cancer cells and demonstrated a higher rate of metastasis than the control group. The cells of the TAC-operated mice also displayed more of the tumor-promoting protein periostin. When researchers added purified periostin to test tube samples, the cancer cells multiplied, whereas reducing the protein lowered the cell proliferation.

The research was supported by the Israel Science Foundation, illustrating the importance of the Technion for Israel’s advancement in the basic sciences.

People who have just learned they have a tumor face heart-wrenching questions such as: is it cancerous? Will it spread?

Article published at ats.org on August 6, 2020.

Metastasis, the spread of cancer cells from the primary tumor to new areas of the body, is responsible for an alarming 90% of cancer-related deaths. But knowing the risk of metastasis early on can help determine the most effective treatment and improve the patient’s outcome.

A research team led by Technion Professor Daphne Weihs of the Faculty of Biomedical Engineering has developed and tested a biomechanical technology to predict whether a tumor is cancerous, and if so, the likelihood of spreading. The method involves seeding tumor-sampled cells on a special synthetic gel that mimics the physiological stiffness of soft tissue, and then observing the cells’ physical impact on the gel. Normal cells do not indent the gels, but invasive cells will forcefully push into the gel’s surface within one to two hours. Quantification of the number of indenting cells along with other measures provide the likelihood of metastasis. The technology was successfully tested on pancreatic tumor cells samples from volunteers at Rambam Health Care campus and on established breast and pancreatic cell lines used for research. The findings were published in the Annals of Biomedical Engineering.

Current methods to determine the risk of metastasis can take days or weeks of valuable time that some cancer patients do not have, but Prof. Weih’s technology helps determine the patient-specific treatment protocol just hours after an initial biopsy. Such swift assessment not only improves the patient’s survival rate but reduces the psychological stress brought on by long wait times.

Working to make their method widely available to patients, Prof. Weihs said, “The invasiveness of cells sampled from tissues is rapidly and quantitatively evaluated using our innovative mechanical invasive assay, which we are currently developing into a clinically applicable technology.”

Since the start of the pandemic, scientists have warned that cancer patients could be at increased risk of serious illness from COVID-19 due to a weakened immune system. But that commonly held belief, reinforced by an early study from China as well as the National Cancer Institute, might be wrong — for certain patients.

Article published at ats.org on September 16, 2020.

In fact, cancer patients, with the exception of those with blood cancers, may not become infected any more than the population at large, and might have the same if not better odds of beating back the most severe symptoms of COVID-19.

Those were the findings of a first-of-its-kind study by scientists at the Technion and Rambam Health Care Campus, who analyzed blood samples from 164 cancer patients undergoing active anti-cancer treatment and 107 healthy Rambam hospital workers to examine changes in the profile of the immune system. They found almost no difference in the rate of developing COVID-19 antibodies. In fact, the rate for the cancer patients was even a bit higher at 2.4% as compared to 1.94% for the healthcare workers. None of the subjects showed symptoms for the coronavirus.

“Our hypothesis is that the different response of cancer patients to the disease is related to the fact that the anti-cancer treatment changes the profile of the immune system,” said Technion Professor Yuval Shaked, head of the Technion Integrated Cancer Center in the Rappaport Faculty of Medicine, who worked alongside Professor Irit Ben-Aharon, director of oncology at Rambam. Specifically, myeloid cells, which are vital to the immune system, are more severely damaged by the coronavirus in the general population than in cancer patients.

The team theorized that cancer treatments may limit the ability of the coronavirus to induce severe inflammation, protecting them from COVID’s life-threatening “cytokine storms,” in which the body’s immune system attacks its own cells rather than fighting off the virus.

The Technion-Rambam team cautioned that their study was small and called for further research. Nonetheless, they hope their work allows cancer patients to breathe easier, as many have delayed treatments to avoid hospitals.

When treating cancer, researchers are always searching for ways to remove cancer cells while minimizing damage to the rest of the body. One possible approach is to find processes unique to cancer cells, and which would allow specific targeting. If such a process can be disrupted, only those cells would be affected.

Article published at ats.org on February 4, 2021.

A process (or absence thereof) can be unique to some types of cancer, and not be present in others. In such a case, we would want a simple way to recognize whether a particular tumor possesses the unique trait or not. The implication of this question is whether the tumor would respond to this or that treatment, allowing us to match a treatment to the patient who is likely to be helped by it, rather than going by trial and error.

Professor Tomer Shlomi’s research group discovered just such a process – one that may be targeted in cancer cells without causing damage to healthy ones, findings that have been published in Cell Metabolism.

Prof. Shlomi is a member of the Henry and Marilyn Taub Faculty of Computer Science, the Faculty of Biology, the Lorry I. Lokey Center for Life Science and Engineering, and the Rappaport Technion Integrated Cancer Center.

The folate cycle is a process essential to DNA and RNA production. As a result, it is highly important to both cancer cells and healthy cells. Because DNA production is a critical stage in cell division, and thus in tumor growth, the folate cycle is a common target for chemotherapy. However, for the very same reason, there are significant side effects to attacking it.

Tomer Shlomi
Professor

There are, in fact, two folate cycles – one happening in the mitochondria (an organelle inside the cell), and one in the cytosol (the fluid that fills the cell). A healthy cell can switch from one to the other. A variety of tumor cells, Professor Shlomi’s group discovered, rely on the cytosolic pathway exclusively. The implication is, if treatment were to target the cytosolic folate cycle, healthy cells would switch to the mitochondrial cycle and would not be harmed, leaving tumor cells to die.

It remains to recognize whether a particular tumor is indeed one in which the mitochondrial folate cycle is non-functional, and here too Shlomi’s team provided. RFC is a transporter protein that regulates intracellular folate levels. Low RFC – low folate. Low folate, the group discovered, is devastating to the mitochondrial cycle. So low RFC tumors are the ones that would be affected by cytosolic cycle-blocking treatments.

Both the pathway that may be attacked, and the way to recognize which tumors the attack would be effective against have thus been found.

Technion scientists have developed a novel method for rapid and accurate sensing of coronavirus without the need to rely on PCR amplification, a technique that makes millions or even billions of copies of DNA so that there is enough material to test. The new technique can identify the presence of SARS-CoV-2 in a sample by counting and quantifying the virus’ RNA molecules with single-molecule precision. This method is not biased by PCR amplification errors, allowing researchers to develop a more accurate clinical diagnostic technique. Researchers have also found that the technique can be used to detect metastatic cancer.

Article published at ats.org on October 21, 2020.

The research was led by Professor Amit Meller and carried out by researchers Dr. Yana Rozevsky, Dr. Tal Gilboa, Dr. Xander van Kooten, and staff scientist Dr. Diana Huttner — all of whom are researchers in the Faculty of Biomedical Engineering — and Professor Ulrike Stein and Dr. Dennis Kobelt from the Max Delbrück Center for Molecular Medicine and the Charité Hospital in Berlin.

Illustration of DNA molecules passing through a nanopore one after the other

RT-qPRC Testing
The most widely used test for COVID-19 is the RT-qPCR test. It requires first collecting a sample from a patient using a swab, “opening” the virus, and extracting RNA from it. In the next stage, called reverse transcription (RT), specific ‘target’ RNA sequences are copied to the DNA form. Finally, this DNA is amplified by a polymerase chain reaction (PCR). Millions of copies are made so that enough DNA is present to be detected, finally leading to a diagnosis for COVID-19.

RT-qPCR testing requires large quantities of special reagents, expensive laboratory equipment, and highly trained professionals. Recent studies have also shown that test results can change from one day to the next and that the massive amplification process can generate significant errors. For these reasons, worldwide efforts are being devoted to developing faster, more affordable, and more accurate tests. This task is particularly challenging in cases where the “viral load” (the amount of viral RNA) in a sample is low and can evade sensing.

Professor Amit Meller
Faculty of Biomedical Engineering

Using Nanopores to “Sense” COVID-19 and Metastatic Cancer
The new method presented by Prof. Meller’s research group relies on original technologies that the lab has developed in the past two decades, using nanofabricated holes (so-called “nanopores”) to sense single biological molecules. The effectiveness of this technology has already been demonstrated in a number of other biomedical uses.

Unlike conventional molecular diagnostics, which require large volumes of samples containing millions of copies of the same molecule, nanopore sensing analyzes individual biological molecules from much smaller samples. A strong electrical field is used to unfold and thread individual DNA molecules through the nanoscopic hole containing electrical or optical sensors. Each molecule that passes through the hole gives a characteristic “signature,” which enables identification and immediate counting of the molecules. This approach opens up the possibility of miniaturising the diagnostic systems while improving the accuracy and reliability of tests.

In an article recently published in ACS Nano, the researchers present two applications of their new method: identifying RNA molecules that signal the emergence of metastatic cancer and detecting coronavirus RNA.

In the first application, the researchers demonstrated the method’s potential for early detection of metastatic cancer by quantifying the levels of MACC1 — one of the primary genes known to signal the formation of a metastatic state. Thanks to its high degree of sensitivity, the new technique successfully quantified the gene’s expression in cancerous cells at the early stages of illness (known as stages I and II) — a challenge that PCR-based technologies failed to meet. Needless to say, the earlier these genetic biomarkers are discovered, the better the chances of successful treatment.

In the second application, the researchers detected the RNA molecules of the SARS-CoV-2 virus using the same approach. Unlike other tests, the new approach avoids introducing “noise” and errors into the system, obtaining a more precise and accurate analysis method.

Commercializing the Technology
With further work, the nanopore sensing system is expected to become a portable device that will make cumbersome lab equipment unnecessary. Technological and clinical research is continuing at the Technion Faculty of Biomedical Engineering, in collaboration with the BioBank at the Rambam Health Care Campus. At the same time, steps are being taken to commercialize the technology in order to make it available for general use as soon as possible.

Breath test from Technion scientist shows promising early results in sniffing out Covid-19 within 30 seconds.

Article published at www.israel21c.org on August 24, 2020.

Could uncomfortable nasal swabs be swapped for a contactless two-second breathalyzer puff to check for Covid-19 infection? Prof. Hossam Haick thinks so.

Haick, a professor of chemical engineering and nanotechnology at the Technion – Israel Institute of Technology, first came to our attention in 2011 for his invention of “NaNose,” which can sniff out cancer, Parkinson’s and Alzheimer’s disease, gastric ailments and more. (Na-Nose is currently being assessed by medical regulators.)

Prof. Hossam Haick, inventor of a breath test for diseases. Photo courtesy of Technion Spokesperson’s Office

When Covid-19 broke out earlier this year, Haick, together with Technion colleague Dr. Yoav Broza, together with researchers from Wuhan, China, began adapting Haick’s “breathalyzer” technology for the novel coronavirus.

The preliminary results look promising.

In a new peer-reviewed study published in the scientific journal ACS Nano, Haick’s sniffer tech correctly identified all positive patients in a clinical trial in Wuhan. The test detects disease-specific biomarkers in the breath with 92% accuracy, 100% sensitivity and 84% specificity, the researchers reported.

The new device, like the original, uses nanotechnology to identify specific volatile organic compounds (VOCs) from the lung that are in the exhaled breath of coronavirus patients.

The Covid-19 breathalyzer could revolutionize testing for the virus – you just need to blow into the device for a couple of seconds from a distance of 2 centimeters and the results come back within 30 seconds.

Fast identification of Covid-positive patients is crucial for contact tracing and is considered the best way, short of a vaccine, to stem community transmission of the virus that has killed more than 800,000 people around the world.

A less invasive system would also make Covid testing more widespread, enabling health departments to identify pre-symptomatic or asymptomatic carriers.

The tests should cost around $2 to $3 a person, Haick added. The self-contained device does not require any additional accessories.

The clinical trial examined 140 people, of whom 49 had previously tested positive for Covid-19. The test identified all the coronavirus carriers. However, it also told seven healthy people they had the virus.

That may sound like a failure, but up to a quarter of current state-of-the-art PCR tests for Covid-19 return false positives as well. From the perspective of doctors tackling the pandemic, false positives are inconvenient but less concerning than false negatives, which can lead to people to assume they are virus-free and as a result spread the virus by mistake.

Like NaNose Medical’s main cancer testing device, its Covid-19 test will also need to be approved by regulators, but Haick expects that to happen faster given the urgency of Covid-19 testing – perhaps as early as six months from now, he says. Still, a larger cohort study will be needed to validate the results.

Haick’s innovation is not the only Israeli test in emergency development today for Covid-19 testing. A “gargle and spit” method is being evaluated on hundreds of patients at Tel Aviv’s Sheba Hospital and has an even higher accuracy rate than Haick’s – up to 95% – which would make it suitable for mass screening at airports, nursing homes and even screening at home, says Prof. Eli Schwartz, head of the trial for Sheba.

Like the breathalyzer, the “gargle and spit” test would be inexpensive and fast – with results analyzed within just one second.

Haick serves as chief technology officer for NaNose Medical in addition to his position at the Technion.

Article published at ats.org on June 2, 2020.

Soon we may not need to retire our protective face mask after a trip to the supermarket. Technion Professor Yair Ein-Eli is developing masks that can be heated to destroy the coronavirus while maintaining their integrity. Reusable, self-cleaning masks are essential for boosting hygiene, mitigating global mask shortages, and protecting the environment.

The new masks contain a heating element of carbon fibers and a USB port for charging. When connected to a low-current cable for less than 30 minutes, the masks heat to between 149 to 158 degrees Fahrenheit and kill viruses and bacteria. “If you are in your car and take your mask off, you can simply connect it to your cigarette lighter charger, then put it back on as if it’s new,” said Prof. Ein-Eli, dean of the Faculty of Materials Science and Engineering.

An expert in battery technology, Prof. Ein-Eli hit on the idea after considering, and rejecting, the notion of adding a battery, as they would make the masks too heavy. He wanted a mask that was convenient, so it needed to be compatible with phone chargers. He and his team experimented with different carbon fibers until finding the right one.

In collaboration with Technion biologists, they have already filed an application for a U.S. patent and are in discussions with companies about commercialization. Prof. Ein-Eli estimates that masks without ports could be updated with his heating mechanism for just 90 cents.

The Need

One of the major obstacles experienced during the global COVID-19 pandemic has been the accessibility to testing. The inability to test the greater population has kept decision makers relying on statistical probability in the absence of hard numbers.Testing is considered key to an effective exit strategy for countries to return to normal economic activity.

Product

An inexpensive kit that will enable a simple home test for COVID-19 with results available in under an hour. The test only requires a saliva sample, reactive material and a thermal cup. Once the protocol is approved by the Health Ministry, it
can be made widely available to the population at large. The home-test kit does not require any special lab equipment

Technology

Lead researcher, at the Rappaport Medical Faculty, Prof. Naama Geva-Zatorsky, has developed a kit using existing materials capable of identifying the genetic material of COVID-19. The team proved that in medium and high concentrations of coronavirus, the test identifies 99% of the cases. The technology is low-cost, rapid, and does not require specialist equipment or lab expertise. In future the test could be adapted to other viruses and pathogens.
The test was developed with the collaboration of colleagues at the Rambam Health Care Center and Meir Medical Center.

Read here for the latest from the Technion.

High schoolers’ robotic platform shuttles supplies to and from the coronavirus ward while controlled remotely by medical staff.

Article published at www.israel21c.or on April 12, 2020.

The battle against coronavirus in Israel just got a helping hand from an unexpected source: the robotics club at the prestigious Hebrew Reali School in Haifa.

Students and alumni of the robotics club, called “Galaxia 5987 in memory of David Zohar,” answered a call from Rambam Medical Center and the Technion – Israel Institute of Technology. In under a week, they developed a robot according to the hospital’s requirements.

The Reali School’s robotics club and alumni with their CoRobot robotic prototype. Photo courtesy of Technion Spokesperson’s Office

The prototype robotic platform, CoRobot, can shuttle supplies to and from the coronavirus ward to minimize the need for medical staff to enter and risk catching the highly infectious virus.

CoRobot can be remotely operated by medical staff using a joystick or a smartphone app. They can see what is happening through the video camera attached to the robot.

CoRobot can transport supplies to patients while minimizing the need for human medical staff to enter infectious wards. Photo courtesy of Technion Spokesperson’s Office

“If the robot will successfully pass its installation at Rambam, in a relatively short amount of time we will be able to build more robots for Rambam and for similar departments in other Israeli hospitals,” says Prof. Alon Wolf, the Technion’s VP for External Relations and Resource Development.

Wolf is also a robotics expert who heads the the FIRST robotics program in Israel. FIRST is an international educational organization that uses robotics competitions to promote entrepreneurship and learning among young children and youth.

FIRST ISRAEL, led by Technion, runs hundreds of groups across the country. According to Wolf, should the robot prove successful, additional FIRST groups across Israel will join the effort.

Technion Prof. Gil Yudilevitch, who leads the Reali robotics program, added that more is in store for CoRobot.

“In the next stage the robot will incorporate a communication system that will include a screen, camera, microphone and speaker, and will be able to move from patient to patient and transmit information to the medical staff in real time. I hope that in the future we will add features that will help with the actual treatment, such as sensors that will check patients’ pulse rates and blood oxygen levels,” he says.