TeachableMedicalNews article 02272024

Teachable moment in classrooms:

  1. cellular basis of life chapter – cell cycle, and phases of mitosis
  2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
  3. cellular basis of life chapter – enzymes are proteins that catalyze chemical reactions
  4. nervous tissue chapter – functions of the neuroglial cells

The news item:  Recently this reporting appeared online:

Novartis drug combo shows promise in childhood brain cancer

An oral drug combination by Swiss pharmaceuticals company Novartis showed promise in treating a subgroup of patients suffering from a common childhood brain cancer in a trial.

 

The article describes a new drug combination for the treatment of childhood brain cancer, namely low grade glioma. The article states that about 1000 children are diagnosed yearly with this brain cancer, and that the study participants were between the ages 1 and 17. The new treatment slowed the cancer progression more than standard chemotherapy.

So, Why Do I Care??  Brain cancer in children is very disruptive to their development and education, and even worse, it can end their lives. In addition, parents, siblings, relatives, classmates all suffer emotional trauma. New treatments that slow the progression of these gliomas promise fewer disruptions and longer survival.

Plain English, Please!!!   First, let’s talk about what a glioma is. Inside our brain and spinal cord there are cells called neuroglia. They support the working of neurons. When mutations cause the neuroglial cells to divide continually, then an abnormal accumulation of neuroglial cells results, thus a glioma forms. The most frequent mutations in gliomas are the ones that activate MEK kinase and the BRAF kinase enzymes. The normal function of these enzymes is to act inside the cells to add phosphate groups to proteins. Those phosphorylated proteins stimulate the start of cell division.

Second, let’s talk about how mutations of the MEK and BRAF kinases contribute to glioma development. Under normal circumstances the kinases are active only during interphase when a growth stimulating factor activates them. The mutations permanently activate the kinases, meaning that they remain active even when there is no growth stimulation signal from the outside of the cell. Think about the thermostat in your house that is periodically turns on your furnace after receiving the signal of dropping temperature in the house. If a malfunction of the thermostat would permanently activate it, then your furnace would be on continually, even when temperature of the house is very warm.  The permanent activation of the kinases causes the constant stimulation of the cell division of the neuroglia cells, and that leads to a mass of neuroglial cells, the glioma.

Third, let’s talk about how the new treatment fights glioma growth.  One cancer fighting drug, Mekinist, has already been used for glioma treatment. Mekinist slows down, inhibits, overly active MEK kinase. The new ingredient is Tafinlar which slows down, inhibits, the work of overly active BRAF kinase. Just like a bicycle that slows down better with a front and rear brake than only with a rear brake. It is this combination of the two brakes, the two kinase inhibitors that showed promising results in the clinical trial described in the article.

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