Cancer, What You May Want to Know

January 31, 2008 at 9:59 am | In Lifestyle, Sciences |

To know early
By Dudi Goldberg (translated from Yedioth Aharonoth, 18 December 2007)

Professor Hadassah Dagani has developed a revolutionary non-invasive method for early detection of beast cancer and prostate cancer.

The sad truth is that the most effective tool in the fight against cancer is early detection; thus the best treatment is—as banal as it sounds—prevention or, regrettably, early detection.

In a large number of cancer cases, no matter the type (excepting a few types of leukemia where the cure is almost certain), by the time metastatic tumors are discovered, the chances for a cure are not high. This is the background necessary to understand the importance of the discoveries by Professor Hadassah Dagani of the Department of Biological Regulation at the Weizmann Institute of Science.

Professor Dagani and her research team developed a very precise yet non-invasive method to detect cancerous growths, even of a small size, using magnetic resonance. The revolutionary method, which has gained FDA approval, is already implemented in several major medical centers in the United States. Besides being very precise, this method reduces the pain associated with an invasive biopsy.

The method even permits assessing the success rates of different cancer treatments at halting tumor development.

Professor Dagani, how does your method work?
The method is based on injecting contrast (a substance that “colors” organs so they can be seen in an MRI) into the patient’s blood stream, and then we follow the contrast with an MRI machine. The rate and pattern of the contrast’s diffusion differs between tumor cells and normal tissue. This method also gives us specific information about microscopic blood vessels that begin to develop in the area of the tumor. This information can also help us forecast the rate of tumor development since the development of blood vessels, which feed the tumor nutrients and oxygen, is necessary for tumor development. Without these “supply lines,” tumor development will slow to a standstill.

How do the blood cells in a tumor differ from blood vessels in normal tissue?
In general, blood vessels in malignant tumors grow in a disorganized fashion and are “leakier” than normal cells; in other words, nutrients enter a tumor at a much higher rate than a normal tissue, so following its progression is clear. An area that the contrast enters much more quickly than other areas is where cancer cells are hiding. By the way, the blood cells of a cyst are leakier than a normal cell but not as leaky as cancer cells.

Does this method work for detecting all types of cancer?
No. We developed this technique several years ago for detecting breast cancer but we then developed a similar method for detecting prostate cancer. We are now testing the method’s effectiveness for early detection of lung cancer and also researching metastatic growths.
Professor Dagani’s method was tested successfully on animals over several years and lately on humans and was also awarded a patent. In Israel, it is utilized in a laboratory in the radiology department at Sheba Hospital (Professor Y. Yitzhak) and in Meir Hospital in Kfar Saba (Dr. M. Shapira).

How do you envision the continuing development of your research?
I believe in the future this will be the accepted method of early detection of all types of cancer. In truth, early detection is the best treatment today.

A “nuclear explosion” against cancer

Professor Hochberg is developing a toxin that will “explode” only in cancer cells

Dudi Goldman (translated from Yedioth Aharonoth)

Professor Avraham Hochberg of the Hebrew University in Jerusalem has dedicated 40 years to studying cancer, of which 12 were spent in intensive study of the mysterious H-19 gene. Hochberg has succeeded in developing a “bomb” that eliminates this cancer gene. Using this “bomb,” he hopes it will be possible to develop a cure for over 30 types of cancers within a few years.

“The H-19 gene is active only in the fetal stages and then it ceases operation,” explains Hochberg, an expert biochemist. “But the gene reactivates and fuels the growth of about 30 types of cancer, when it plays a central role in tumor development. It appears that this gene is not just a side effect of the cancer; in fact, it causes the disease. It allows cancer cells to survive, permitting tumor development and metastasis.”

What did you do after you had discovered and studied the gene?
We discovered that we could use the gene’s activation mechanism to activate a toxin (which he calls an “atomic bomb) that would explode exclusively in cancer cells. We took the toxin from the diphtheria virus, which is a terrible virus against which we are all vaccinated in childhood. When the diphtheria toxin happens upon a regular cell, it’s like a dud bomb—nothing happens. But when it chances upon a cancer cell, it becomes a bomb that destroys the cancer cell. It’s like a Trojan horse. The diphtheria toxin stops production of cellular proteins and thus essentially causes the cell’s death.

Have you tested this treatment in animals?
We are already in the process of human trials. We have finished the first stage of clinical trials for bladder cancer and the second stage will begin in about a month in seven Israeli and American hospitals. It also appeared that there were no side effects to the treatment.

If the trials go well, when do you believe the treatment will hit the market?
Within three to five years. We are now testing the efficacy of the treatment for pancreatic cancer, ovarian cancer, liver tumors resulting from colorectal cancer, and bladder cancer. But this treatment could be effective for over 30 other types of cancer. The final plan is to develop a treatment personalized to each patient based on his form of cancer, through advanced screening. We have developed screening technology that can identify even solitary cancer cells. Understanding the cell’s activation mechanism led to developing the treatment that destroys cancer cells without harming healthy cells at all. The treatment is personalized based on the type of tumor and the specific expression of the gene in the tumor cells.

Cancer cells and their neighbors
Dudi Goldman (translated from Yedioth Aharonoth)

In contrast to most cancer researchers, Professor Weitz decided to think differently and to focus instead on the “neighbors” of cancer cells.

Professor Yitzhak Weitz, formerly Dean of the Tel Aviv University Faculty of Life Sciences and currently head of the Center for the Study of Cancer Biology, works off the assumption that cancer cells, like people, interact with their environment. Weitz, a prize-winning researcher, has found that the interaction between cancer cells and their neighboring healthy cells drives the process creating malignant tumors.
In his groundbreaking research, Professor Weitz focuses on molecules involved in creating colorectal cancer tumors in the liver and neuroblastoma tumors in bone marrow and in the lungs. The goal of his research is the development of drugs to stop the activity of these molecules in order to prevent creation of tumors or at to at least slow the process appreciably.
“Everything I have tried to do for years has been in order to learn more and more about the capabilities of these “terrorist” cancer cells,” says Weitz.

How can these interactions harm the body?
It’s high treason. Our cells and our molecules must act on our behalf, not against us. There are, for example, cells that fight invading microbes with certain secretions. It turns out that cancer cells can take advantage of these secretions produced by a healthy body to become violent.

So now that we have this information, how can we take care of these “terrorists”?
There are now drugs that treat the interaction between the cancer cells and their micro-environment. I hope that in the future, we will know more about the interactions that cause tumor cells to metastasize. Additionally, malignant tumor cells can circumvent many roadblocks (i.e. resist treatments) and take more circuitous routes to reach their target and metastasize. So we need to put up more roadblocks. Treatment with one drug is not sufficient. The question is whether cancer cells have infinite options to circumvent these roadblocks and exhibit drug resistance. In my opinion, no. The more we know about cancer cells’ evasion mechanisms, the better off we are. And in this regard, the research is not finished and we are all, really, trying to learn about all of these terrorists’ techniques.

In your opinion, what lies ahead?
I believe that in the future, cancer, in all its forms, will go from a deadly disease to a chronic disease. In other words, a permanent disease with which one can live. And maybe in the future, we will learn how to eradicate it completely, as happened with some forms of childhood leukemia; in the past most children died from the disease, but now the vast majority survive.

Activating Cancer
By Dudi Goldberg (translated from Yedioth Aharonoth)

Professor Haim (Howard) Cedar’s research may lead to the development of medicines that will prevent cancer before it develops.

Today, there are 200 recognized types of cancer and treatments effective against one form are often ineffective against other types of cancer. Perhaps this is one reason for slow progress made in eradicating the disease. On the other hand, research conducted by Professor Haim Cedar, at the Hebrew University Medical School, added new insight to understanding the mechanism that activates cancers. This research has the potential to lead to the development of treatments that would prevent the development of many forms of cancer.

For many years, Professor Cedar, the winner of the 1999 Israel Prize, has researched genes and gene regulation. Cedar, incidentally, is the father of director Joseph Cedar (“Beaufort”), who won the best director award at the Berlin international film festival. His current research, in conjunction with Ravid Straussman, Ilana Keshet, Meirav Hecht, and Yeshayahu Schlesinger, made waves and was published in Nature Genetics, a respected scientific journal.

What, really, is gene regulation?
The genes we inherit from our parents are present in each of our cells. However, there are also regulatory mechanisms—known as silencing mechanisms—that determine which genes will be expressed and which will not. It’s like a switch in the “off” position.

How does this relate to cancer?
Our body is constantly exposed to harmful influences that could cause genetic mutation and thus cancer. When there is a mutation, the body attempts to fix it and resist it. But we discovered something serious: Cancer manages to cripple the repair mechanism. In other words, genes in normal cells are silenced because of cancer.
This is a type of activation mechanism imprinted in some people’s genomes. It is set at the early stages of life and begins to function when the cancer process begins. A situation thus arises in which hundreds of genes are silenced by this mechanism.

Would someone know if he had this system in his genome?
Unfortunately, no. It’s like a computer. A person has a preset, orderly genetic activation system that works well. But some people have another, inactive activation mechanism. When the cancer process begins, this other mechanism, which silences genes, kicks into action causing cancerous behavior. Cancer is the result and combination of a local incident (a genetic mutation) and a global incident—the activation mechanism in the realm of gene regulation.

So that means that some people are “cancer-ready”?
Unfortunately, that’s correct. And that happens long before the mutation.

What new approaches could result from this research?
Currently, most cancer treatments utilize substances that poison the cancer cells to protect the body from a hostile takeover. The problem is that this type of treatment harms normal cells as well. I hope that our research will pave the way to find a general cure that will prevent the “silencing.” In other words, it will operate against silencing the genes. Theoretically, there is hope for an all-encompassing treatment for cancer that will be effective in the preventive stages (before the disease actually strikes).