Straight Talk about Mesothelioma, a blog series created by Michael T. Milano, M.D., Ph.D., a radiation oncology specialist, as a resource for mesothelioma patients and their loved ones.


Dealing with a Mesothelioma Diagnosis: The Outlook

A cancer diagnosis is one of the most frightening things a person can experience in his or her lifetime. What’s worse is that some cancers are deadlier than others – and mesothelioma fits into this category. About 3,200 people are diagnosed with mesothelioma each year. The 5-year survival rate for people who have mesothelioma ranges between 5 and 10 percent. Yes, unfortunately, it’s that low.

As with many cancers, the earlier the diagnosis, the better the chances of living longer. Still, people with mesothelioma diagnosed in earlier stages may only live about 19 – 21 months.

Current treatment options for mesothelioma typically include surgery, chemotherapy, and/or radiation. However, these therapies only serve as ways of managing mesothelioma. For most patients, they cannot cure the disease.

With New Research Comes New Hope

Scientists are working hard to find new mesothelioma treatment options. Previous research focused on how manipulating the growth factor called “vascular endothelial growth factor,” or VEGF, could be used to manage cancer. Found on the surface of many types of cancer cells, VEGF encourages the growth of new blood vessels. However, scientists think that another growth factor, vascular endothelial growth factor receptor, or VEGFR-2, may play a stronger role in encouraging communication within endothelial cells and might therefore play a more active role in cancer development.

This type of treatment is called “antiangiogenic therapy” — a kind of treatment that focuses on designing drugs that will starve the blood supply that feeds cancer cells.

But in order to understand what antiangiogenic therapy is and how it works to fight cancer, it’s important to understand more about how tumors develop and how cancer spreads. This can be a complicated topic, and for a long time, scientists didn’t quite understand how it worked. Luckily, recent advances in medicine have helped scientists get a better grasp on how tumors grow, which may prove beneficial in figuring out new ways to treat mesothelioma and other cancers.

What Is Angiogenesis & What Does It Have to Do with Cancer?

In the same way that normal, healthy tissues in the body rely on blood vessels for nourishment, tumors also require a blood supply in order to survive, grow, and spread. This process usually means that new blood vessels must form in order to feed the tumor. The formation of new blood vessels is what scientists call “angiogenesis.”

However, not all angiogenesis leads to cancer. In fact, angiogenesis occurs naturally in the bodies of healthy individuals and plays an important role in helping the body to grow, heal, and reproduce. And just as our government operates on a system of checks and balances, the body works to achieve its own level of internal balance when it comes to angiogenesis. This delicate system of balances is controlled by special proteins called “growth factors” and “inhibitors.”

As the name implies, growth factors aid in the generation and formation of new vascular tissue or blood vessels. They do this by sending signals to the body that encourage the formation of new blood vessels. Meanwhile, inhibitors have an opposite effect, working by either blocking the growth of blood vessels or preventing them from developing further. This same checks and balances system must work properly in order to make sure that cells and tissues in the body grow when they are supposed to grow and stop when they’ve grown enough.

In a healthy person, the balance between growth factors and inhibitors means that cells don’t need to send signals to the body that they need another blood supply. Instead, they can remain at rest.

On the other hand, an imbalance results in the overproduction of growth factors, or inhibitors. Overproduction of either protein can cause disease to develop. When it comes to cancer, the body may have an imbalance in which it produces too many growth factors or not enough inhibitors to prevent the development of new blood vessels. Scientists now know that tumors can stimulate angiogenesis by encouraging the recruitment of growth factors and somehow preventing inhibitors from regulating that process. Angiogenesis is vital to the growth and metastasis of the cancer, as the cancer relies on a blood supply to feed the tumors.

How Do Growth Factors & Inhibitors Affect Tumors?

Growth factors and inhibitors bind to special areas, called receptors, on the surfaces of endothelial cells that line the lungs. These receptors each have a special shape that is uniquely designed to fit the shape of a certain chemical protein.

If a chemical doesn’t have the right shape that fits the receptor on the cell’s surface, then the protein can’t attach or bind to the receptor. This means that that protein won’t be able to send signals to the cell to encourage certain reactions within the body. However, when a protein like a growth factor or inhibitor makes contact with a receptor that has a complementary shape, it will bind to the receptor and initiate a series of reactions. These reactions are a form of communication that the cell uses to encourage the formation of new blood vessels.

Now that scientists have learned more about how cancer cells use signals to communicate with the body to encourage angiogenesis, they are using their knowledge to research further how manipulating angiogenesis may be able to save cancer patients’ lives.

What Were the Results of the Angiogenesis Study on Mesothelioma?

At the Hyogo College of Medicine in Nishinomiya, Hyogo, Japan, researchers investigated whether the effects of several proteins — angiostatin, endostatin, and VEGFR-2 — could actually block the growth of cancer cells in the endothelium. Ultimately, they wanted to find out what affect these proteins would have on cancer cells.

In order to do this, scientists experimented with human mesothelioma cancer cells in which they used viruses to transfer the DNA needed to generate the receptors for antiangiogenic drugs. Three unique mesothelioma cell lines were made, each using a different virally-injected angiogenic receptor. Growth of endothelial cells (necessary for formation of blood vessels) was compromised when 2 or more cell lines were grown together. Dr. Shuji Kubo and colleagues wrote that, “Antiangiogenic gene therapy targeting the different [ways angiogenesis occurs] should be better for long-term success by presumably reducing the risk of resistance [to cancer treatment].”

While this study is promising, more research is needed. “Anti-angiogenic therapy cannot eradicate tumors by itself and therefore, is kind of second line maintenance therapy. Therefore, long-term and combination treatment regimens will be essential…” researchers wrote.