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Fighting Cancer

These 5 Israeli advances could transform cancer treatment

By Ben Hartman

Many of the world’s most effective cancer treatments have roots in Israeli research. The work taking place in Israeli labs today may lead to lifesaving treatments years in the future.

Here are five promising areas Israeli researchers are studying in their quest for better cancer detection and treatment.

Mutant reeducation camp and the fight against ovarian cancer

Mutant reeducation may sound like the plot of the next “X-Men” movie, but for a team of Israeli researchers it could be central to finding new treatments for ovarian cancer, an especially deadly disease because of the difficulties of early detection.

In a program at Israel’s Weizmann Institute of Science financed in part by the Israel Cancer Research Fund (ICRF), Dr. Varda Rotter is looking for ways to fight the disease on the molecular level using a protein known as the “king of tumor suppressors.”

The protein, p53, stops the formation of tumors. But when p53 mutates, it makes cancer cells more malignant and boosts their resistance to drugs. Rotter and her team have identified a small number of molecules that are able to “reeducate” mutant p53 and restore it to its role scanning for damaged DNA and stopping the development of tumors. They are also looking for methods to reeducate the mutant p53 to fight and eradicate mutant cells.

“We are trying to find a way to convert or reeducate the mutant p53 to its role as the ‘guardian of the genome,’” Rotter said. “It will reeducate the p53 into the right type of p53 and will show that under such circumstances there is a reduction of cell death in treated cells.”

Rotter hopes her team’s research will result in methods that can be applied along with immunotherapy to give women with ovarian cancer a better chance of beating the disease.


Restoring infertility? Hit the restart button.

Dr. Jacob Hanna believes stem-cell treatments hold promise for restoring fertility to cancer survivors whose chemotherapy has rendered them infertile. (Weizmann Institute)

For many cancer patients, surviving is just the first part of the battle. They often face serious lifelong problems, such as infertility or the loss of healthy tissue that is difficult to regrow.

The key, Dr. Jacob Hanna of the Weizmann Institute believes, lies in stem cells. Stem cells are early-stage cells that are capable of dividing into infinitely more cells and have the potential to become different cell types, such as bone, skin or muscle and can help repair damaged tissue.

Hanna is using ICRF funding to research ways to take cells from healthy areas of the patient’s body and turn them back into induced embryonic stem cells. Because the stem cells in Hanna’s model would come directly from the patient’s DNA rather than from a donor, the tissue would not face rejection.

Hanna believes stem-cell treatments are going to become reality in the next 20 years, and restoring fertility to infertile cancer survivors could be one major benefit.

“We want to make mature human cells in the Petri dish. If this is successful, it could be a major breakthrough for solving infertility problems in general, not only for women who underwent chemotherapy,” Hanna said. “This could stop doctors from avoiding doing chemotherapy because they’re worried about damaging the patient’s fertility,” Hanna added. “It would allow them to give longer treatment or stronger regiments.”


To fight brain cancer, think small. Very, very small.

Glioblastoma, a particularly aggressive and deadly form of brain cancer, carries a very grim prognosis: Patients have a median survival time of about 15 months from the day of discovery.

Tel Aviv University researcher Dr. Dan Peer is seeking ways to fight brain tumors using a targeted nanoparticle platform to transport drugs directly to the sites that need treatment rather than a more general chemotherapy or surgery. Targeted treatments the size of a nanometer – a millionth of a millimeter – would minimize the effects on the rest of the body by targeting only the cancer cells and avoiding healthy cells nearby.

The delivery vehicle would be RNA – ribonucleic acid, whose main role is to carry instructions from DNA. By binding the RNA to a nanoparticle platform, researchers hope to bypass the hurdles that usually thwart drug delivery by specifically targeting the problem areas of the tumor.

By carrying the drugs specifically to the cancer cells and not to the healthy ones, the treatment will have fewer adverse effects and toxicities for the patient while maximizing the drugs’ therapeutic effect.

“If we can somehow diminish the spreading of the tumor and improve diagnosis and therapeutic effect,” Peer said, “that will be beneficial for the patient.”


Fighting carcinomas: Rehab for non-malignant cells

Dr. Ruth Scherz-Shouval is studying how tumors metastasize by recruiting non-malignant cells to help them overcome the human immune system. (Weizmann Institute)

For tumors to expand and metastasize, they “recruit” non-malignant cells in the tumor microenvironment and get them to work for them and help them evade the immune system. Dr. Ruth Scherz-Shouval of the Weizmann Institute is studying the tumor microenvironment to determine how non-cancerous cells get reprogrammed to act against the body and support the tumor rather than defend the body against the tumorous growth.

“The cells of the microenvironment don’t have the mutation that causes cancer cells to become cancer cells – yet they do things they are not supposed to do,” she said. “We are interested in understanding how this happens.”

Scherz-Shouval compared treatment in the microenvironment to rehabilitating a nonviolent offender who can still be put on the right path – unlike a hardened felon (the tumorous cell) who is too far gone to save. She hopes her research, backed by the ICRF, will lead to a more generalized way to target cells in the microenvironment that will complement current cancer treatments and give patients a better chance at recovery.


Wanted: A better way to fight leukemia

Most leukemia treatments today focus on chemotherapy, steroid drugs and stem cell transplants. But Ben-Gurion University of the Negev researcher Roi Gazit is on the hunt for more effective, targeted treatments.

“Our models will help to better specify which treatment may suit a specific type, and even sub-type, of the disease,” said Gazit. “Unfortunately, there is no one-size-fits-all treatment for leukemia. That’s why we need tailor-made models to fit the treatment to the disease.”

Gazit is focusing on how to develop targeted treatment of cancer cells using hematopoietic stem cells – stem cells used in cancer treatment because of their ability to divide and form new and different kinds of blood cells.

The research involves taking primary cells – cells cultured directly from a subject – and turning them into malignant leukemia growth inside mice. By examining how the leukemia develops, Gazit is exploring ways that hematopoietic stem cells may be deployed to arrest the leukemia.

The research models his lab is using, part of a project supported by ICRF, could help scientists develop more types of immunotherapy and more ways to use stem cells to combat leukemia.

“With any new information we can gain better understanding, which translates into better treatment,” Gazit said.


Award-winning Israeli cancer researcher says immunotherapy is the ‘future’ of treatment

By Sean Savage/JNS.org

CAP: (l to r): Consul General of Israel in New York Dani Dayan, the Weizmann Institute’s Prof. Yosef Yarden and Israel Cancer Research Fund President Rob Densen at the consul general’s residence. Credit: Perry Bindelglass.

A rapidly aging population and increased environmental risks have led cancer to overtake heart disease as the leading cause of death in parts of the Western world. Researchers remain a long way from eradicating cancer, but several new treatments may offer hope. On the cutting edge of cancer research in Israel is Prof. Yosef Yarden of the Weizmann Institute. Earlier this year, Yarden was awarded the Israel Prize – the state’s highest honor – in life science research.

Born in 1952, Yarden received degrees in biology and geology from the Hebrew University of Jerusalem, and a molecular biology doctorate from the Weizmann Institute. He is known for his discovery of the function of an enzyme that strengthens the chemical signals that lead cells to become cancerous, especially in breast, ovarian and lung tumors. Much of his work is centered on EGFR and HER2, which belong to a family of growth factor receptors that play a crucial role in tumor progression. Yarden’s findings have laid the foundation for the creation of new cancer treatments such as immunotherapy, which uses the body’s immune system to help fight cancer.

JNS.org spoke with Yarden while he was in New York attending a fundraiser for the Israel Cancer Research Fund, which supports Israeli scientists in their efforts to find a cure and treatments for cancer.


JNS: Could you explain the nature of the research that led to you receiving the Israel Prize?

Yosef Yarden: I became interested in the connection not only between genes and cancer, but also specific molecules called growth factors.

Cancer tumors need to collaborate with the human body. To them it is a hostile system and environment. They find a way to recruit the human body or host; they attract blood vessels for oxygen and sugars, minerals, vitamins, etc….so they can sustain themselves. Somebody needs to take care of them and feed them. The way they do that is by sending signals to the human body, telling them that they are a new organ here and to take care of it, [to] supply the oxygen and all of the goodies.

The growth factors are what tell the body that this is a new organ here – you’ve never seen it before, but that organ is growing very rapidly, kind of like an embryo. Those are the growth factors.

We started a way to block the growth factors, because that is kind of the key of collaboration between the tumor and the host.


JNS: How does your research relate to immunotherapy?

Yosef Yarden: Immunotherapy is at the very heart of my research. One clear way to void the growth factors is to use antibodies. Antibodies are molecules–we can engineer them to get rid of growth factors. Now, we can engineer the antibodies to make them suitable for injecting into human patients. Sometimes they are very effective in blocking cancer.


JNS: You believe that immunotherapy is preferable to traditional forms of combating cancer, such as chemotherapy and radiation. Why?

Yosef Yarden: Radiation is one way to slow down the proliferation of cancer cells. Unlike most cells in our body, that are resting and rarely divide, cancer cells are rapidly dividing. Chemotherapy and radiation slow down the rate of proliferation, but it comes with an enormous cost. There are some cells that are rapidly dividing and this affects them, such as hair and skin cells, gastrointestinal cells, red and white blood cells etc….it is very hard for patients.

The new generation of immunotherapy antibodies are in fact biological molecules and the body naturally uses them, so they come with very mild side effects. The future is very much in immunotherapy.


JNS: What impact has the Israel Cancer Research Fund (ICRF) had on your career, and throughout Israel?

Yosef Yarden: In many aspects, Israel is considered a superpower in the field of cancer research worldwide–proportionally, in terms of breakthroughs, volumes of findings, pharmacology of cancer and even the success of cancer treatment of patients in Israel.

ICRF is committed to basic research, which we know is a precondition of actual early detection and prevention of cancer. The ICRF serves as a major player in the Israeli arena that deals with cancer research and early detection research.

The ICRF has supported me in the past 30-plus years. I always remember my first grant from the ICRF in 1988, which helped me in my first critical steps early in my career. They gave me money for seven years, which is still today my longest period of grant money. It is very critical, timely and very generous.


JNS: What do you love about being a research scientist?

Yosef Yarden: I believe it is a great time to be a cancer researcher today, with all the new promising breakthroughs. When I began, we were just shooting in the dark. Cancer is such a difficult disease to model, to mimic and study. Since it may develop so slowly in the body, initially dormant, nobody can detect it. Then it emerges sometimes when we are old, and it attacks us.

I think one major milestone in my career was the completion of the human genome project around the millennium. It helped us enter a new era in cancer research. It gave us, in a way, a roadmap of cancer and a listing of all of the mutations.

The tricky thing about cancer is, it is very individualized. A particular person with kidney cancer may be different than another person with kidney cancer. Now we understand that, and we have to tailor therapy and treatment to every patient according to their cancer genome, not even the human one. The cancer genome is essentially a copy of a human genome, except it comes with several mutations. The mutations push cancer forward. And they are a major target of our research.

For more information on the Israel Cancer Research Fund, contact Connecticut-area Director David Kweskin at (203) 321-1006 or david.kweskin@icrfonline.org.


Supporting cancer research in Israel

Established in 1975, the Israel Cancer Research Fund (ICRF) is the largest charitable organization in North America solely devoted to supporting cancer research in Israel. With chapters in Stamford, New York, Los Angeles, Chicago, Toronto, Montreal and Jerusalem, ICRF has provided more than 2,400 grants to outstanding cancer researchers whose laboratories are located in all of the leading research institutions, universities and hospitals across Israel.

For more information on the Israel Cancer Research Fund, contact Connecticut Area Director David Kweskin at (203) 321-1006 or david.kweskin@icrfonline.org, or visit icrfonline.org.

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