What If We Could Cure Solid Cancers Without Scars?

Kate Hitchcock, MD, PhD


August 16, 2021

"The absence of [EN-1-positive fibroblasts] not only limited scar formation but also unexpectedly resulted in the regeneration of hair follicles and appendages." —Drs Naik and Konieczny, 2021

During Histology in the first year of medical school and Pathology in the second, fibroblasts were presented as pretty uninteresting cells. Yeah, they were always there in the background, gamely holding everyone's stuff together. But my professors, who could wax rhapsodical to the extent of 60.5 uninterrupted minutes on the UBL domain of yeast protein Rad23, never had too much to say about fibroblasts. I was left with the impression that these cells are to the body what the color gray is to the world: present, necessary, rarely the center of conversation.

What a surprise it was to me, then, to have to worry about the personal habits of fibroblasts all day every day in my career. We are getting pretty darned good at curing many cancers that would have killed people when I was in college. One interesting side effect of this development is that people go on living. That means that the damage done to their bodies both by the cancer and by our treatments survives with them.

Chemotherapy, radiation therapy, and surgery all cause their own types of fibrosis, and by and large it is permanent.

All oncologists may therefore be interested in an offering in the April 23, 2021, issue of Science, in which Piotr Konieczny and Shruti Naik of NYU have provided an excellent description of our current understanding of these (it turns out) extremely interesting cells and their habits with regard to forming scar tissue in the body.

I am left wishing that the authors had been professors of mine, but more importantly with a much more detailed understanding of this process that is so critical to our patients' health, and I commend their writing to you.

As a sneak preview, the authors describe recent work on how fibroblast behavior is affected by a transcription factor called En-1, which gets fired up in response to certain mechanical stresses and seems to govern the tendency of our bodies to create scar tissue where we would really prefer restoration of the normal tissue architecture.

As they point out, our ancestors couldn't afford the downtime this would have entailed, so we evolved as animals that repair the damage fast and get the show back on the road. It turns out that there are different types of fibroblasts not just in different organs but in different sites in the same organ. All seem to share this En-1 pathway as a determiner of scar tissue and fibrosis formation. And when it's turned on, fibrosis and scar tissue are going to be laid down.

That has implications for such diseases as pulmonary fibrosis and cirrhosis, but also for our cancer patients, and sheds some light on the variable responses of different organs to tumor- and treatment-induced damage.

Interestingly, cells with En-1 upregulated behave differently in fetuses than in adults, which raises the question of whether manipulation of this pathway could restore our ability to generate new, healthy organs as some other species do.

Anyone else seen interesting news on the topic of preventing scarring and fibrosis?

Please join the discussion below, but if you need to communicate with me offline, you can reach me at

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About Dr Kate Hitchcock
Kate Hitchcock, MD, PhD, is a radiation oncologist, biomedical engineer, and retired aircraft carrier driver who grew up as a Wyoming cowgirl. When she is not at the hospital, you can find her with Carolyn, Mary, Tyler, Nick, Marlee, and Colby the barking dog, enjoying the natural splendor of the great state of Florida. She thinks you should visit sometime and try to solve the puzzle of why the natives have so carefully shunted all of the tourists toward the House of Mouse. Connect with her on Twitter: @hitchcock_kate


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