Cancer cells enter a ‘diapause’ state when attacked by chemo, producing a compound that blocks autophagy, allowing them to reawaken when the danger has passed and they have developed genetic changes rendering the chemo worthless.
Researchers affiliated with the Princess Margaret Cancer Center and the University of Toronto and led by Catherine O’Brien, MD, PhD, and Miguel Ramalho-Santos, PhD, have showed (1) that ALL cancer cells – not just a few – enter a slow growing, lethargic state when under threat from Chemotherapy drugs.
In the study, they reviewed colorectal cancer, a cancer where chemotherapy often fails and 4 drugs in combinations like FOLFOX and FOLFIRI must be used just to get some response. Now we know why.
The cells hibernate, waking up when the drug threat has gone. Actually, ‘hibernate’ isn’t quite the correct description. The right word is diapause, which indicates ‘a reversible state of suspended embryonic development triggered by unfavourable environmental conditions’, said O’Brien.
Worse, in this state, the cancer cells make a compound that prevents cancer cell death (autophagy). When the researchers blocked this compound, the chemo killed the cancer cells. However its protective effects bought the cancer cells time allowing them to form genetic changes and resist the drugs.
About 18 months ago Professor Charlie Swanton of UCL reviewed 71 cancer drugs approved by US regulators in the 12 years to 2016 and showed they had generated an average increased survival of just 2.1 months of extra life.
*****
Reference
- Colorectal Cancer Cells Enter a Diapause-like DTPState to Survive Chemotherapy ”