Can we treat breast cancer by targeting a mutation in the cancer cells?

TeachableMedicalNews article 11122022

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 – cell division is regulated
4. female reproductive system chapter – anatomical location of mammary ducts

The news item: Recently the following reporting appeared online:

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The article states that the newly approved breast cancer treatment, Piqray, is for the HR+, HER2 – advanced breast cancer cases. The article also states that this new drug is targeting PIK3CA mutations.

So, Why Do I Care??  There are over 280,000 new breast cancer diagnoses each year in the USA. Deaths from breast cancer is estimated to be over 43,000 each year in the USA. Every new treatment regimen reduces the number of deaths, or increases survival time. In addition, a drug that targets mutated cancer cells also lowers the side effects, because only the mutated cells are attacked.

Plain English, Please!!! First, let’s talk about what breast cancer is. In all cancers the normal cells of a particular portion of the body transformed, so they suddenly gain the ability to divide without control. In the case of breast cancer the epithelial cells of the inner lining of mammary ducts transform into cancer cells. The mammary duct cells divide in controlled fashion to fill gaps where cell died in the duct.

Second, let’s talk about why cancer cells divide without control. Our cells normally divide by going through the steps of interphase, prophase, metaphase, anaphase, telophase, the process that divides the nucleus. That process is stimulated by chemicals made inside the cell.  PI3K makes chemicals that stimulate cell growth in interphase, and progression through the cell. PI3K is a complex of proteins that add a phosphate group to organic chemicals, and that addition makes those chemicals active stimulators. Imagine that the street that a cell has to travel to complete cell division has traffic light. PI3K is changing the light to green when it makes a stimulator. The mutated version of PI3K is called PI3KCA, and that protein makes too many stimulators. On that street of cell division the lights are always green, and, so, the cell completes many cell divisions without stopping.

Third, let’s talk about how does Piqray slows division of cancer cells. The overactive PI3KCA can be slowed down by preventing the addition of the phosphate group to the stimulators.  The pharmaceuticals that do that are called kinase inhibitors. Piqray is a very special kinase inhibitor, because it acts only on PI3KCA. Once PI3KCA is slowed down, the number of green lights on the street of cell division go back to normal, and frequent cell division are no longer possible.