August 2011: A new treatment: Israeli researchers have successfully created the first computerized genome-scale model of cancer cell metabolism which can be used to predict which drugs are lethal to the function of a cancer cell’s metabolism.

Prof. Eytan Ruppin of Tel Aviv University’s Blavatnik School of Computer Science and Sackler Faculty of Medicine and his colleagues Prof. Eyal Gottlieb of the Beatson Institute for Cancer Research in Glasgow, UK, and Dr. Tomer Shlomi of the Technion have a new treatment that selectively targets cancer cells, leaving other cells in our bodies unharmed.

By inhibiting their unique metabolic signatures, explains Prof. Ruppin, cancer cells can be killed off in a specific and selective manner. The efficacy of this method has been demonstrated in both computer and laboratory models pertaining to kidney cancer. Because the researchers’ new approach is generic, it holds promise for future investigations aimed at effective drug therapies for other types of cancer as well. The results were recently published in the journal Nature.

Lethal to cancer, safe for other cells: The ability to specifically target cancer cells is the holy grail of cancer research. Currently, many cancer drugs are designed to target any proliferating cells in the body — and while cancer cells certainly proliferate, so do healthy cells, such as hair and gut lining cells, the growth of which are essential to the body’s overall health. This explains why many cancer treatments, including chemotherapy, have adverse side effects like nausea and hair loss.

Targeting the metabolism of the cancer cell itself may be one of the most effective ways forward. Cancer cells have a special way of metabolizing nutrients for growth and for energy. This makes cancer cell metabolism essentially different from that of a normal cell.

The researchers’ computer model is a reconstruction of the thousands of metabolic reactions that characterize cancer cells. By comparing it to a pre-existing model of a normal human cell’s metabolism, they could distinguish the differences between the two. They could then identify drug targets with the potential to affect the specific, special characteristics of cancer metabolism.

To test their predictions, the researchers chose to target cells from a specific type of renal cancer. “In this type of renal cancer, we predicted that using a drug that would specifically inhibit the enzyme HMOX, involved in Heme metabolism, would selectively and efficiently kill cancer cells, leaving normal cells intact,” Prof. Ruppin stated. Their computer model led them to hypothesize that the Heme pathway was essential for the cancer cell’s metabolism.

In an experimental study led by Prof. Gottlieb’s lab, the researchers were able to verify this prediction in both mouse and human cell models, and to study these metabolic alterations in depth.

An all-around treatment model: Metabolism is a large and complex network, built on thousands of reactions. It is beyond the human capability to fully understand, let alone predict how such a complicated system works, stated Prof. Ruppin. Now, by allowing researchers to simulate the effects of a disorder, computer models are helping researchers to predict the efficacy of potential drugs and treatments. Though the predictions should always be verified in a lab or clinic, this method is highly cost effective and leads to exciting opportunities for accelerating future drug developments.

While the first model was built to characterize a specific type of cancer, this approach can be applied in the future for creating models for other types of cancer. “This is the next big challenge for us,” stated Prof. Ruppin. “We are going to continue to build models for other types of cancer, and seek selective drug therapies to defeat them.” Their multidisciplinary approach requires both the predictions of a computer model and the findings of experimental clinical trials, and may lead to the faster development of more selective and effective cancer treatments.

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July 2011: Researchers at the Weizmann Institute may have found a way to make cancer therapy better, and yet also less expensive. One of the latest attempts to boost the body’s defences against cancer is called adoptive cell transfer, in which patients receive a therapeutic injection of their own immune cells. This therapy, currently tested in early clinical trials for melanoma and neuroblastoma, has its limitations: Removing immune cells from a patient and growing them outside the body for future re-injection is extremely expensive and not always technically feasible.

Weizmann Institute scientists have now tested in mice a new form of adoptive cell transfer which overcomes these limitations while enhancing the tumour-fighting ability of the transferred cells. The research, reported recently in the professional journal Blood, was performed in the lab of Prof. Zelig Eshhar of the Institute’s Immunology Department by graduate student Assaf Marcus and lab technician Tova Waks.

The new approach should be more readily applicable than existing adoptive cell transfer treatments, because it relies on a donor pool of immune T cells that can be prepared in advance, rather than on the patient’s own cells. Using a method pioneered by Prof. Eshhar more than two decades ago, these T cells are outfitted with receptors that specifically seek out and identify the tumour, thereby promoting its destruction.

In the study, the scientists first suppressed the immune system of mice with a relatively mild dose of radiation. They then administered a controlled dose of the modified donor T cells. The mild suppression temporarily prevented the donor T cells from being rejected by the recipient, but it didn’t prevent the cells themselves from attacking the recipient’s body, particularly the tumour.

This approach was precisely what rendered the therapy so effective: The delay in the rejection of the donor T cells gave these cells sufficient opportunity to destroy the tumour. If this method works in humans as well as it did in mice, it could lead to an affordable cell transfer therapy for a wide variety of cancers.

Chemotherapy, while considered an effective cancer treatment, also brings debilitating side effects such as nausea, liver toxicity and a battered immune system.

A new way to deliver this life-saving therapy to cancer patients has been developed by researches at Tel Aviv University. Dr. Dan Peer of Tel Aviv University’s Department of Cell Research and Immunology and Prof. Rimona Margalit of the Department of Biochemistry and Molecular Biology led the research.

The breakthrough technology consists of a nano-sized vehicle with the ability to deliver chemotherapy drugs directly into cancer cells while avoiding interaction with healthy cells, increasing the efficiency of chemotherapeutic treatment while reducing its side effects.

Dr. Peer explained the vehicle is very similar to a cluster bomb. Inside the nano-vehicle itself are tiny particles of chemotherapy drugs. When the delivery vehicle comes into contact with cancer cells, it releases the chemotherapeutic payload directly into the cell. According to Dr. Peer, the nano-medical device can be used to treat many different types of cancer, including lung, blood, colon, breast, ovarian, pancreatic, and even several types of brain cancers.

The finding was recently reported in the journal Biomaterials.

A Sweet Payload to Trick Cancer: The key to the drug delivery platform is the molecule used to create the outer coating of this cluster nano-vehicle, a sugar recognized by receptors on many types of cancer cells.  When the nano-vehicle interacts with the receptor on the cancerous cell, the receptor undergoes a structural change and the chemotherapy payload is released directly into the cancer cell which leads to more focused chemotherapeutic treatment against the diseased cells.

Because the nano-vehicle reacts only to cancer cells, the healthy cells that surround them remain untouched and unaffected by the therapy. The nano-vehicle itself, is made from organic materials which fully decompose in the body once it has performed its function, making the treatment safer than current therapies.

Clinical Trials Coming Soon: This drug will be an improvement on anything currently on the market. Delivering chemotherapeutics directly into cancerous cells themselves is not only more potent, but also much safer. Drs. Peer and Margalit are working with ORUUS Pharma in California, which has licensed the “cluster bomb” platform from the university and can ensure a quick transition from the lab to clinical trials, which should begin in two years or less.