A new analysis on how asbestos-related tumors grow may lead to more effective research and treatments of malignant mesothelioma.
Researchers at Australia’s Flinders University found malignant mesothelioma tumors demonstrate vasculogenic (vascular) mimicry — the process in which tumors make their own blood vessels.
Tumors promote their own growth by growing blood vessels that reach into surrounding tissues instead of waiting for the outside of the tissue to grow blood vessels into the cancer cells.
Oxygen and nutrients from blood vessels allow cancer cells to develop into secondary tumors.
“[Vasculogenic mimicry] is something that was first described in melanoma, and which since then has been found in some other tumors, such as some breast cancers, but not every great cancer can do it, and the tumors which can, behave more aggressively,” Sonja Klebe, an associate professor of molecular medicine and pathology at Flinders, told Asbestos.com.
What Does Vascular Mimicry Mean for Mesothelioma Research?
Mesothelioma is a highly aggressive cancer.
It carries an unusually long latency period — or the amount of time between initial asbestos exposure and diagnosis — of 20 to 50 years.
The aggressiveness can depend on several factors, including stage of the disease and cell subtype. Epithelial cells are the most common, accounting for up to 70 percent of all mesothelioma cases, while sarcomatoid cells are the least common but most aggressive.
The research from Flinders University and previous studies suggests tumors capable of vasculogenic mimicry are more aggressive, which may explain the limitations of bevacizumab and other chemotherapy drugs when treating malignant mesothelioma cells.
“The fact that there is more than one way for the tumor to get its nutrients makes it more resistant to anti-angiogenic therapies, which may explain why bevacizumab is not as effective in mesothelioma as was hoped,” Klebe said.
Klebe first considered the idea of vasculogenic mimicry in mesothelioma tumors after receiving clinical samples containing clusters of differentiation 31 (CD31), a protein that plays a key role in the removal of white blood cells from the body. CD31 also acts as a vascular marker to demonstrate the presence of endothelial cells in histological tissue sections.
This can help evaluate the process through which new blood vessels form from pre-existing vessels, called angiogenesis.
Klebe also grew mesothelioma cells from the pleural fluid of patients under different incubation conditions.
“So I had two levels of evidence that suggested to me that vasculogenic mimicry is real in mesothelioma,” she said.
Klebe and her team have shown vasculogenic mimicry of mesothelioma tumors in an animal model and a few more clinical samples.
These findings could potentially revolutionize future mesothelioma research, changing the way scientists and doctors target mesothelioma cells.
Potential Changes in Mesothelioma Treatments
Current mesothelioma tumor treatments target blood vessels that grow into the cancer, not the other way around.
Klebe believes one potential approach would be to target both types of vessels to starve the tumor of blood supply and key nutrients.
Doctors often use anti-angiogenesis drugs in combination with standard chemotherapy drugs for mesothelioma such as cisplatin.
Researchers currently are testing cediranib, an experimental anti-angiogenesis drug, for its ability to inhibit tumor growth in patients with advanced pleural mesothelioma, the most common type of mesothelioma. The drug blocks the vascular endothelial growth factor (VEGF), an essential element of tumor blood vessel growth.
Anti-angiogenesis drugs are especially beneficial to late-stage or advanced mesothelioma patients because the drugs can potentially keep the disease from spreading to other organs.
The recent findings about the vasculogenic mimicry function of mesothelioma tumors offers valuable insight into the rare cancer.
However, Klebe believes a cure for mesothelioma is still far off because of the inability to detect the tumors early enough.
Doctors diagnose 3,000 cases of mesothelioma each year in the U.S. The cancer primarily affects men 60 years and older with a history of occupational asbestos exposure.
Because of the rarity of the cancer and its long latency period, doctors often misdiagnose mesothelioma as a less serious condition or as a different form of cancer like lung cancer. Once symptoms, such as persistent cough or difficulty breathing become nagging or debilitating, the cancer is likely in the later stages and more difficult to treat.
But as researchers continue to learn more about mesothelioma tumors, Klebe believes they are closer to finding treatments that will significantly prolong life with fewer impacts on quality of life.
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