TeachableMedicalNews article 04282022

Teachable moment in classrooms:

  1. cellular basis of life chapter – concept of one gene, one protein
  2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
  3. cellular basis of life chapter – mitosis (somatic cell division) is stimulated from outside of the cell
  4. tissue chapter – epithelium types in the respiratory system
  5. respiratory system chapter – epithelial lining of the airways

The news item:  Recently this news item appeared online about a new treatment for lung cancer:

New hope for patients with lung cancer

FDA approves Tabrecta™, a new treatment option, for adult patients with metastatic non-small cell lung cancer

The report states that lung cancer is the leading cause of death among cancers, and that there will be about 228,000 new diagnoses in the USA each year.  The article also states that the drug Tabrecta helps patients to fight non-small cell lung cancer (NSCLC), that the drug works especially well against cancers driven by a Met exon 14 skipping mutation, and that each year about 4,000- 5,000 people in the USA are diagnosed with this subtype of NSCLC.

So, Why Do I Care??  Lung cancer is a deadly disease, so finding new treatment options improves the chance of survival when traditional treatments may not work, and, thus, lengthens the survival time after the diagnosis. Another reason to care is that this drug acts specifically on cancer cells that carry a particular genetic change, so this ability improves targeted attack on cancer cells, and avoid attacking the normal cells of the body.

Plain English, Please!!!  First, let’s talk about just what NSCLC is. The NSCLC name represents a type of relatively slow-growing lung cancers that start in the mucous glands of the airways, or in the simple squamous epithelium of the alveoli. Several mutations make the NSCLC cancer grow faster, and subtypes of NSCLC are named after their particular mutation.

Second, let’s talk about what an oncogene is. It sure sounds menacing that we carry cancer causing genes in out cells. The truth is that the oncogenes are normal genes that cause cancer only if they suffer mutations. The mutations in the oncogene DNA cause a change in the function of the protein, and that changed function causes cancer.

Third, let’s talk about why Met is an oncogene.  The normal Met protein sits in the cell membrane, like a doorbell sits in the doorframe. Other proteins can bind to the Met protein, push this doorbell, and the ringing (the signal) heard inside the house (the cell) will make the cell divide. One mutation that makes Met an oncogene is the Met exon 14 skipping mutation. Picture the Met gene as a book, and then each chapter is an exon (stretches of DNA needed to come together to form the book). The Met gene has 21 chapters altogether. This mutation cuts the entire chapter 14 out of the book, so it changes the instruction carried in the book.  This mutation leads to a shorter than normal Met protein, and that shorter Met protein will malfunction, because the short Met protein will act like a doorbell that is stuck, and the constant “ringing” of the doorbell makes the cell divide faster. To put it all together, the Met exon 14 skipping mutation makes the NSCLC cells divide faster, which pushing them to spread in the body faster and further.

Fourth, let’s talk about how the drug Tabrecta works to slow down the mutated Met protein. The Met protein doorbell uses chemical energy from inside the cell. The drug Tabrecta sticks to the inside of the Met protein doorbell, and cuts off the chemical energy source, so the doorbell stops “ringing”, and the cell stops dividing.