Recently received a valuable prospective from T_A in a recent discussion on the difficulties of hormonal adaptations of PC. He drew my attention to the view of cancer as a "complex adaptive system" (CAS). This is clearly a valuable perspective or lens through which to look at the bigger picture of cancer and therapeutics.
Attached below is link to a slide show on this topic from Arizona State. It is easy to follow and get the main ideas without having to swim in the deep end of cellular signaling pathways! Some main ideas I will highlight. (I don't mean to sound like a lecture, etc. I just think it is very useful for us.):
The difference between "complicated systems" and "complex adaptive systems" is that merely complicated systems (like man-made machines or networks) have low intrinsic freedom. 2) Have predictable behavior and thus 3) Behavior is fixed and not capable of autonomous evolution. While complex adaptive systems, such as the weather & climate, stock markets, geopolitics, predator-prey systems, pandemics and cancer have 1) Emergence - new properties emerge from interactions of simpler units. 2) Thus cannot be reliably predicted. And 3) The "whole is more than the sum of its parts". Therefore 4) New and unexpected patterns of interactions shift the system to new and different (unpredictable) states.
Quoting: "The behavior of all complex biological systems is defined by Darwinian evolution" -Including: Variation (heterogeneity in tumor clones and sub-clones); Evolvability (adaptation to selective pressures including the tumor micro-environment, the microbiome, the immune system responses and to our treatments); Ultimately changing fitness to adapt and survive leads to the "relentless" emergence of new properties and adaptive clonal evolution in cancer.
To me this shows that we need to prepare to adapt and continue to change up the game, hopefully staying one step ahead of evolutionary adaptation in the cancer. Fixed strategies may be doomed to failure, but we can learn new ways to change things up. That also "emerges" from the ever shifting landscape of research and trials. Fight on my friends.