A recent EMBO Molecular Medicine paper describes how scientists investigated the damage that taxanes inflict on human hair follicles.
The researchers found that taxanes are toxic to specialized niches of cells at the base of hair follicles.
These niches contain cells that divide rapidly and are essential for producing hair.
In further experiments, the team found that CDK4/6 inhibitors, a class of drug that halts cell division, can prevent the damage that taxane inflicts in the hair follicle.
In addition, the CDK4/6 inhibitors worked in a way that did not inflict further damage on the hair follicle.
“When we bathed organ cultured human scalp hair follicles in CDK4/6 inhibitors,” says lead and corresponding study author Talveen S. Purba, Ph.D., “the hair follicles were much less susceptible to the damaging effects of taxanes.”
Purba is a research associate in the Centre for Dermatology Research at the University of Manchester in the United Kingdom.
Chemotherapy induced hair loss
“Taxanes are a leading cause of severe and often permanent chemotherapy induced alopecia,” write the authors, who go on to discuss the need for new and effective strategies to prevent this type of hair loss.
Hair loss is a very distressing and sometimes enduring side effect of chemotherapy.
Chemotherapy induced alopecia can damage an individual’s body image, self‐esteem, and quality of life, especially when the hair does not grow back.
The authors note that as many as 8% of people likely reject chemotherapy because of this “psychosocial burden.”
They hope that the findings will spur the development of skin medicines that doctors can apply to the skin of their chemotherapy patients to reduce hair loss.
Treatments that temporarily slow or stop cell division in hair follicles could help to boost the effectiveness of hair preserving treatments such as scalp cooling, which can be “unsatisfactory and difficult to predict.”
The findings could also help to develop treatments to prevent hair loss on other sites of the body, such as eyebrows, beards, and pubic hair, which individuals may also value for “cosmetic, cultural, religious, and psychosocial,” reasons.
CDK4/6 inhibitor protected hair cells
For the new study, Purba and colleagues focused on two taxanes — paclitaxel and docetaxel — that doctors use in the treatment of solid tumors, such as in the breast and lung.
The team tested the drugs on hair follicles they cultured in the laboratory under conditions that were as natural as possible. The hair follicles came from the scalps of consenting patients.
The hair follicle is a “mini organ” that is easy to remove whole and readily lends itself to laboratory experimentation.
The team found that paclitaxel and docetaxel induced massive damage to cell division processes and triggered cell death in follicle cells that are essential for hair production.
The follicle cells that underwent damage included transit amplifying cells, which divide rapidly, and their progenitor, or stem cells. Impairment of this cell population likely explains the “severity and permanence of taxane chemotherapy induced alopecia.”
When they administered palbociclib, a CDK4/6 inhibitor to the organ cultured hair follicles before exposing them to paclitaxel, the researchers found that it protected without inflicting further damage.
Proof of principle
The authors conclude that their findings are proof of principle that this type of cell protective therapy can limit the damage that taxane chemotherapy can induce in hair follicles.
The team points out that there is an urgent need for more work on how to prevent hair loss in cancer patients.
In addition, there is a need to find out how to regenerate hair follicles in order to help those who have already lost their hair permanently following chemotherapy.
There are many long standing questions that still demand answers. Why is it, for instance, that chemotherapy hair loss is more severe in some people than others, despite all receiving the same drug and dose?
Also, why do some chemotherapy treatments and drug combinations result in mild hair loss, while others cause severe or permanent loss?
“Despite the fact that taxanes have been used in the clinic for decades and have long been known to cause hair loss, we’re only now scratching the surface of how they damage the human hair follicle.”
Talveen S. Purba, Ph.D.