REMISSION, RELAPSE. Then what?

Happy

Far too many ovarian cancer histories go like this.  First, the cancer is diagnosed, often by accident (OVCA symptoms are notoriously subtle), and found to be in an advanced state (Linda was stage 3C, indicating that the original tumor had spread throughout her abdomen.)  The first therapeutic step involves so-called “debulking surgery” – all visible traces of the cancer are cut out.  Next comes “adjuvant chemotherapy”, involving a cocktail of drugs that, hopefully, will kill any remaining cancer cells.  Workhorses among these drugs often are platinum-based.  Normally this puts the patient into “remission” – that is, no trace of the disease can be detected.  (Remission often is monitored by periodic determination of the level of the protein CA 125 in the blood.  “Normal”, which varies considerably, ranges from 0 to 30 or so; Linda was at 650 when diagnosed and at 6 after treatment.)

In remission the patient can live a normal life.   Her hair grows back, she regains strength and mobility, she can be happy.  However, after a few months or years in all too many cases remission is gradually lost.  In Linda’s case her CA 125 count remained at 6 for about two years.  Then, one month it rose to 8.  No problem, right?  The next month it was 15.  The cancer was coming back.

Apparently the cisplatin-based drug cocktail was effective initially, but had left behind a few cancer cells that were “immune”, rendering it futile to repeat the original chemotherapy.  In Linda’s case another selection of drugs was tried, resulting in only a short, partial remission.

Well, researchers at the University of Michigan may have discovered a way to deal with this apparent immunity.  They found that fibroblasts (a type of cell involved in connective tissue) located in the tumor’s microenvironment acted to prevent buildup of platinum in the cell.  They also found that immune T cells could pry open the fibroblast barrier, thereby allowing the platinum poison in to kill the cell.  (Mice, again, of course.)

  My reading of this is two-fold.  Maybe administering T cell based immunotherapy along with standard platinum-based chemo would wipe the cancer out in one fell swoop.  Barring that, maybe T-cells would make it possible to use the same drugs after an initial remission, thereby prolonging remission indefinitely.  More I cannot say; there are important parts of these two articles that I simply don’t understand.

And here is something else I don’t understand: how in heck are we supposed to regard the process of  “relapse”?  I have written about “cancer stem cells”; are there such, and how do they operate?  Also I keep reading about the accelerated rate of mutation in cancers, presumably making it difficult to eradicate the beast completely before it changes.  Now I read that an army of misguided fibroblasts promote relapse by combating cisplatin.  Are all of these things true?  If so, God help us.

http://www.genengnews.com/gen-news-highlights/t-cells-help-reverse-ovarian-cancer-drug-resistance/81252753/

http://www.siasat.com/news/reversing-chemo-resistance-ovarian-cancer-immune-cells-961322/