Can a genetic mutation of cancer cells be exploited to kill them?

TeachableMedicalNews article 03282021

Teachable moment in classrooms:

1. chemical basis of life chapter – DNA structure as double helix
2. cellular basis of life chapter – DNA replication during mitosis
3. cellular basis of life chapter – DNA mutation of a gene usually diminishes protein function
4. digestive system – anatomy of pancreatic duct (origin of most pancreatic cancers)
5. reproductive system – anatomy of ovary (surface epithelium is the origin of most ovarian cancers)

The news item:  Recently this article appeared online about a new pancreatic cancer treatment:

FDA approves drug for treating pancreatic cancer

Health regulators clear AstraZeneca and Merck treatment for disease projected to kill 46,000 Americans this year.

The article states that Lynparza has been approved for the treatment of ovarian cancers with BRCA mutation, and this approval is now extended to pancreatic cancers with the same mutation. The article also states that the BRCA mutation hinders fixing DNA damage, that Lynparza is a PARP inhibitor, and that 46,000 Americans die yearly because of pancreatic cancer.

So, Why Do I Care??  Pancreatic cancer has a very low survival rate, because the diagnosis usually happens in the late stage of the cancer. A new drug will likely increase survival rates among those 46,000 patients.

Plain English, Please!!!   First, let’s talk about the BRCA mutation. When cells undergo mitosis (cell division) the DNA is copied (replicated), so the new cell can have as much DNA as the starter cell. During replication the two strands of the DNA double helix are pulled apart, and a new DNA strand is created (copied) along each original strand. If the original DNA has brakes in it, the copying will introduce mistakes into the new DNA strand. The BRCA protein repairs those breaks before a copying mistake can happen. Think about BRCA protein as a spell-checker on your computer that connects word parts that you, by mistake, typed in as separate words. The mutations in the BRCA gene cause the BRCA protein to repair fewer DNA brakes. When that spell-checker is turned off your writing will have many spelling errors. Without that BRCA protein spell-checker the accumulating DNA mistakes change the cell from normal to a cancerous cell. Many ovarian cancers, breast cancers and pancreatic cancers are caused by BRCA mutations.

Second, let’s talk about PARP. Even cancer cells would die with too many spelling errors in their DNA. As it turns out, cancer cells rely on a back-up spellchecker called PARP that cuts out and then repairs the mistakes in the DNA sequence. PARP is made up by a group of proteins. It is the repair activity of those PARP proteins that keeps alive the cancer cells with BRCA mutations.

Third, let’s talk about how Lynparza acts. Now that we know that the BRCA mutant cancer cells rely on PARP to stay alive, it makes sense that if we could inhibit PARP action, then those BRCA mutant cancer cells could no longer survive and divide. Lynparza acts as a PARP inhibitor because it cements PARP onto a single place on the DNA, and doesn’t allow it to move on to repair many misspellings. Lynparza also slows down the speed repair action of PARP. Therefore, Lynparza treatment is expected to slow cancer cell division, and, thus, extend survival rate.