French Study Reveals Potential Mesothelioma Treatment Target
October 31, 2018
A team of French researchers led by Dr. Christophe Blanquart has identified a substance that may better define the severity of malignant pleural mesothelioma (MPM) in the body and provide clues to more effectively manage the rare cancer.
Brain-derived neurotrophic factor, as the name indicates, is a protein found in the brain. BDNF is a growth factor and also appears in other tissues in the body.
“It seems that BDNF could be a prognostic marker for MPM patients,” Blanquart told The Mesothelioma Center at Asbestos.com. “The level of BDNF in pleural fluids could reflect the severity of disease.”
The study was published October 11 in Molecular Cancer.
Physicians often use biomarkers in blood or other body fluids to diagnose the extent of cancer and its response to treatment.
Researchers also use these biomarkers to identify possible new targets for treatment.
There are no well-accepted biomarkers for malignant pleural mesothelioma. The discovery of links between BDNF and MPM is a step in addressing this challenge.
Importance of Growth Factors for Managing MPM
Tumors often produce growth factors that help cancer cells multiply and spread. Some existing cancer treatments target these proteins.
Different cancer types produce an excess of distinct growth factors. A drug targeting only one growth factor won’t work for all cancers.
Some tumors can mutate and find ways around a drug that blocks only one particular growth factor.
This is why continued research is vital for designing better therapies for all cancer patients, including people diagnosed with MPM.
BDNF appears to act as a growth factor for MPM cells, and according to the study, it can be detected in pleural fluids surrounding the lungs.
BDNF Offers Clues for Solving MPM Angiogenesis
Some growth factors help tumors create new blood vessels. The influx of blood, oxygen and nutrients through these vessels spurs cells to multiply.
This process is called angiogenesis, and it gives cancer cells a pathway to migrate and create new tumors in distant tissues.
“Our preliminary data suggest a function of BDNF in angiogenesis induced by pleural fluids from MPM patients in vitro and that a BDNF blocking strategy inhibits this effect,” Blanquart said.
This effect was tested in the lab. The next step for the researchers is to study this approach in animal models.
“Indeed, additional research, notably on in vivo models, is required to confirm this hypothesis.”
Blocking Blood Supply to Improve Treatments
Existing therapies could be combined with an anti-BDNF molecule to target angiogenesis in MPM, according to the researchers.
This may improve efficacy of currently approved drugs, although the authors stress this is speculative. More research is needed to test these ideas.
There is good precedent for this approach. According to the American Society of Clinical Oncology, there are more than a dozen angiogenesis inhibitors.
These medications are used in combination with chemotherapy to treat some colorectal, kidney, lung, thyroid, advanced breast, stomach, pancreatic and liver cancers as well as sarcomas, lymphomas, myelomas and astrocytomas.
BDNF for Diagnosing and Tracking MPM
In order for a biomarker to be useful for diagnosing and tracking cancer, it needs to have good sensitivity and specificity.
This refers to how well the biomarker avoids or limits false-positive and false-negative results.
False positives occur when the test indicates a person has the disease when they do not, resulting in stress and additional diagnostic procedures that are unnecessary and potentially harmful.
False negatives occur when a test shows a person does not have the disease when they do have it. This can result in treatment delays and more advanced, harder-to-treat cancer.
It is possible combining BDNF with other biomarkers may improve MPM diagnosis and treatment.
SMRP and fiubulin-3 are other potential MPM biomarker proteins currently under study by several research groups.
“The characteristics of BDNF, sensitivity and specificity, are too limited to be used alone for the diagnosis of MPM,” Blanquart said. “However, additional studies need to be carried out to evaluate the combination of BDNF with SMRP and/or Fibulin-3.”