Definitely Different, Destructive Differentiation

In the last few posts, I talked about skin cancers and when discussing cutaneous squamous cell carcinoma (cSCC) I mentioned levels of differentiation. To recap, differentiation is the level to which cells look like normal cells of the same type and perform their intended function. Cancer does not just appear on the body like, poof, now you got cancer. It starts from normal cells that begin to function out of step with what they are supposed to be doing. It only takes a few mutations then the cell divides faster, or doesn't die when supposed to and can begin to spread. 

During the first stages of this movement, the cancer cells look very similar to the cells they arose from (the squamous epithelium in this case). As the mutations continue, the cells look less and less like their originators. They may be undeveloped or misshapen, and be multiplying too quickly or with another cell function gone awry. As this happens, it becomes harder and harder to see the cells microscopically. This is one of the ways they can track where a metastasis came from, if well differentiated then by examination it can be seen from which tissue this arose. Breast tissue looking cells in liver cancer? Probably originally breast cancer. Prostate tissue looking cells in the lungs? Probs started in the prostate. 

The more poorly differentiated the cells become, the less likely they are to stay in place. To the example of cSCC, the squamous epithelial cells don't normally penetrate the basal layer, however when the cells don't resemble their originators, this can happen more easily. More differentiation also generally means faster cell division meaning more growth and more gene errors. 

What I just learned here, and that is the point after all though it does make a lot of sense, is that treatment can be made less effective due to poor differentiation. Not the differentiation itself but if the pathologist is not able to identify the type of cancer immediately, there may be delays in treatment or the initiation of ineffective or even harmful treatment. Google cancer treatments or look at the indications for many of the newer-ish targeted therapies. For XYZ cancer with ABC negative mutations and FGH this and PRW positive something else receptive to CVB. Even more basic than that, certain cancers are resistant to some chemo drugs that may be first line therapy for what the cancer was misdiagnosed as. 

Either way, differentiation can play a large role in the diagnosis and management of malignancies. One of the more interesting things I have read about cancer treatment in a while is the research into therapies that try to reverse differentiation. That is to return a wayward cancer cell to its normal state. I found two articles that look at cancer treatments to restore differentiation, how cool. Seriously radical. It is also really comical to image metastatic prostate cancer that spread to the skin, being cured through differentiation, then the patient ends up with a prostate on his temple. Yes I know thats not how it works but humor me. 

I really like to read about what people think of to try in the fight against cancer, and diseases in general. Thank goodness for smart people, how else would I find anything to write about? I hope you kinda enjoyed that and if you did please share this. If you didn't, share this with someone you hate. Try the Occasionally Preposterous Podcast to listen to my mellifluous tones for a few minutes. Love y'all. 

References

Cancer cell differentiation heterogeneity and aggressive behavior is solid tumors by Jogi et al., in the Upsala Journal of Medical Sciences May 2012.

Differentiation therapy and the mechanisms that terminate cancer proliferation without harming normal cells from Cell Death & Disease by Enane et al., in 2018. 

 

Image and a hunk of information above from Differentiation Therapy: A promising strategy for cancer treatment by Yan and Liu from the Chinese Journal of Cancer 2016.

Poorly Differentiated Neoplasms by Hainsworth and Greco from the Holland-Frei Cancer Medicine. 6th Edition.

Small Molecule-Induces Differentiation as a Potential Therapy for Liver Cancer by Zhang et al., in Advanced Science March 2022.