Saturday, September 19, 2015

An aspirin a day...keeps melanoma at bay....and makes immunotherapy work better!!!!

We have long known that NSAID's (nonsteroidal anti-inflammatory drugs) decrease the risk of many cancers.  For instance:

"NSAID's, including aspirin, decrease the incidence and mortality from colon cancer in humans by 45% to 50%."  DuBois, Cancer Research, 56(4), 1996.

That's old, y'all!!!  More recently, (well, in 2012) researchers in Denmark looked at the medical records of 18,000 people from 1991-2009 and found that: "people who had taken aspirin, ibuprofen and related painkillers -- especially at high doses and for years at a time -- were less likely to get skin cancer, compared to those who rarely used those medications.  The findings add to growing evidence that long-term use of the medications, known as nonsteroidal anti-inflammatory drugs, or NSAIDs, may help protect people against skin cancers, including melanoma, the deadliest type."  Common painkillers tied to lower skin cancer risk

And now....there's this from Zelenay et al., Cell, September 2015:  Cyclooxyenase-dependent tumor growth through evasion of immunity

Which sounds very fancy....but here's the deal:   To back up a step -  NSAIDs block an enzyme, cyclooxygenase (also called: COX1 and COX2).  Blocking those enzymes, blocks the production of prostaglandins.  Soooo..... These researchers used genetically modified mice to research the role of prostaglandins in blocking immune rejection of tumors.  Aspirin and similar NSAIDs stop the production of prostaglandins, thereby allowing immune cells to kill tumors more easily and enhancing the checkpoint inhibitors like anti-PD1 (nivo/opdivo and pembro/keytruda), anti-PDL1, and anti-CTLA4 (ipililmumab).  They note:
  • Prostaglandins in tumors interferes with immune cell function.
  • Blocking cyclooxygenase in tumors restores immune cell function.
  • The cyclooxygenase blockers (NSAIDs) increase the action of checkpoint inhibitors.
  • This mechanism is shared by mouse and human tumor systems.
My thoughts:  While you can find conflicting reports regarding effects of NSAIDs and this latest study was done with real ratties (ie the 4 legged kind!!), the benefit of COX inhibitors in the form of NSAIDs sounds like a pretty common sense, low risk, and reliable finding to aid patients' results from immunotherapy.  I am certain that my study did NOT control for NSAID use, but I imagine it is a pretty rare anti-PD1 patient who does not utilize ibuprofen to deal with arthralagias and other aches and pains the therapy produces!!  I know I certainly lived on advil and benadryl to deal with my rashes and beat up joints.  Of course, the next step will be an examination of the application in human ratties....  So, time will tell.  But, I think I'll keep taking my ibuprofen....unless Bentie makes me switch to aspirin!!!

Love - c

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