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A New Drug to Treat Solid Tumors, Including Mesothelioma

Solid tumors come in a variety of types, from some of the most common cancers like breast, colorectal, and lung cancers, to those that are very rare, like mesothelioma. Battling solid tumor cancers is challenging, and researchers are always working to develop newer, better ways to slow, stop, and kill cancer cells in these tumors.

Most recently, a class of drugs that targets an enzyme that is crucial in the proliferation of solid tumor cells has shown great promise. Specifically, a drug called CB-839 may be an exciting and effective new target for solid tumor cancers. Already showing safety and early efficacy in phase I clinical trials involving mesothelioma and other cancer patients, this drug has been fast tracked and may provide a hopeful solution for so many struggling with these cancers.

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Solid Tumors and Mesothelioma

Solid tumors are growths that do not contain liquids or liquid-filled cysts. Many different types of cancer are classified as having solid tumors, although these tumors are not always cancerous; they may be benign and non-malignant. Cancers that are not characterized by solid tumors include blood cancers, like leukemia. The most common types of solid tumors include breast, lung, colorectal, and prostate cancers.

Even though it is not common, mesothelioma is a type of solid tumor. Although it is categorized as a solid tumor cancer, one reason mesothelioma is difficult to treat is that it rarely forms one or two large tumors. Instead, it develops as multiple, smaller solid tumors that spread readily throughout the chest cavity. This makes targeted surgeries a challenge because it is nearly impossible to remove every single tumor.

Lung cancer is another type of solid tumor cancer and is one of the most common types of cancers in the U.S. Mesothelioma is almost always caused by asbestos exposure, but there are many potential causes of lung cancer. Asbestos can be a trigger or even a cause of lung cancer, and developing solid tumor treatments and medications are important for the battle against both mesothelioma and asbestos lung cancer.

Glutamine and Tumor Growth

Cancer cells within malignant solid tumors have unique metabolic pathways, different from healthy cells. For example, these cells rely much more on glycolysis, the breakdown of glucose for energy, than healthy cells do. Another important pathway for cancer cells is the conversion of glutamine to glutamate and other metabolic products. Glutamine is an amino acid, one of the building blocks of proteins. Together, glucose and glutamine provide solid tumor cells with most of the material needed to grow, proliferate, and create new cancer cells.

Glutaminase Inhibitors

The enzyme that is crucial in converting glutamine to metabolic products that cancer cell use to proliferate is glutaminase. Inhibiting this enzyme is a promising strategy for slowing or stopping the growth and proliferation of solid tumor cells and in treating many types of malignant cancers. Research has already found that if glutamine can be removed from the tumor environment, growth slows to a stop and tumor cells will even die.

While removing glutamine may not be a realistic way to target cancer cells, stopping the action of glutaminase, the enzyme that uses glutamine, may be. Another reason to target the enzyme instead of removing glutamine is that glutamine is important in the growth of T-cells, human immune cells.

By restricting the action of glutaminase, which breaks down glutamine, novel drugs may cause glutamine to build up, allowing the immune system to grow and strengthen. A drug that could do both of these could be a two-factor treatment for cancer: blocking the tumor’s metabolic pathway and stimulating the immune system to better fight off the cancer.

CB-839 Showing Promise in Treating Solid Tumors

There is a drug made by Calithera Biosciences that may be able to do just that. Called CB-839, this solid tumor target is currently going through clinical trials to determine safety and tolerability in human patients. CB-839 is a glutaminase inhibitor, so it works by stopping the action of the enzyme and blocking the important glutamine metabolic pathway that allows tumors to grow and develop. This blockage also has the effect of increasing the available glutamine that would otherwise be taken up by the tumor. The proliferation of glutamine stimulates and activates T-cells in the immune system.

Preclinical research with CB-839 found that the drug could stop the growth of cancer cells and even kill cancer cells in a variety of solid tumor types. The preclinical trials included animal studies, which have shown great promise in stopping tumor growth and in tolerability. The doses of the drug needed to kill and stop cancer cells from growing were well tolerated by the animals.

These preclinical studies have led to a phase I clinical trial with human patients. Part 1 of the trial included patients with any type of solid tumor, while part 2 was limited to those with non-small cell lung cancer, triple-negative breast cancer, specific types of gastrointestinal tumors, renal cell cancer, and mesothelioma. The phase I trial produced results sufficient to move onto phase II trials to be conducted in 2017.

CB-839 Fast Tracked by FDA

Calithera announced in June of 2017 that the U.S. Food and Drug Administration (FDA) granted Fast Track status to CB-839. The designation is specifically for the treatment of metastatic renal cell carcinoma and in combination with a chemotherapy drug called everolimus. The Fast Track designation is supposed to speed the process of developing and bringing to market drugs that show promise in treating life-threatening illnesses, like mesothelioma and other solid tumors. That this status has been given to CB-839 demonstrates its important potential for helping cancer patients.

For patients living with solid tumor cancers, especially those that are so difficult to treat like mesothelioma, the promise of a new drug provides hope and a potential solution. For mesothelioma patients, in particular, a new drug that may be effective means so much. Rare cancers like this one get less attention and less research focus than those that are more common. A drug like CBB-839 offers mesothelioma patients a reason to hope that a real treatment is possible in the future.

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